cardiovascular-agents and Aortic-Diseases

Penetrating aortic ulcers (PAUs) are an entity within acute aortic syndrome. They often remain undiagnosed and are found incidentally or when they become symptomatic. Management is currently guided by clinical judgment. This review aims to identify indications for treatment and inform management.. We searched PubMed for studies on the management of PAUs. The outcome measures were mortality, progression and resolution of symptoms.. This review incorporates 27 studies involving 1356 patients with PAU. Data was available regarding symptoms for 1213 patients (494 symptomatic, 719 asymptomatic). Overall late mortality for PAUs was found to be higher than 30-day mortality. Early mortality was higher for symptomatic patients as compared to those with asymptomatic PAUs. Early mortality was lowest for PAUs treated with endovascular interventions (5%), followed by PAUs managed medically and highest following open surgical management. Indications for treatment included symptoms, progression/instability, aortic diameter >5 cm, concomitant aortic pathology or pleural effusion. 13% of patients managed conservatively at initial presentation demonstrated progression and were considered for intervention subsequently. 9% of patients required reintervention after initial endovascular surgery.. Endovascular treatment, if anatomically suitable, should be considered as first line treatment for symptomatic PAUs. Patients with asymptomatic PAUs, if associated with high-risk features such as PAU diameter >20 mm, PAU depth >10 mm, aortic diameter >42 mm, concomitant pathology, morphological change or an infective etiology, should also be considered for intervention. Small asymptomatic PAUs with no high-risk features may be managed conservatively but must undergo regular surveillance.

Topics: Aortic Diseases; Cardiovascular Agents; Clinical Decision-Making; Disease Progression; Endovascular Procedures; Humans; Risk Assessment; Risk Factors; Treatment Outcome; Ulcer; Vascular Surgical Procedures

To date, thoracic endovascular aortic repair (TEVAR) for type B aortic dissection is favorable, but TEVAR for type B intramural hematoma (IMH) remains uncertain. There are numerous clinical (e.g., refractory pain) and radiologic (e.g., IMH thickness) factors that are reported to be associated with IMH progression, challenging the treatment for high-risk type B IMH with high risk factors in clinical practice.. The objective of the study was to perform a systematic review of clinical studies to investigate outcomes of TEVAR + best medical treatment (BMT) and BMT in the treatment of high-risk type B IMH.. The online databases of PubMed, MEDLINE, EMBASE, CNKI, Google Scholar, and Cochrane as well as some journals majoring in endovascular surgery and interventional therapy were searched on September 1, 2017. Observational studies that reported the effect of TEVAR and BMT on type B IMH were included. Two independent reviewers performed methodological assessment and data extraction. Random and fixed effects models were used to calculate pooled effect size estimates. A sensitivity analysis was also carried out.. In all 6 included studies, the total number of patients with type B IMH was 237 and 123 patients received TEVAR + BMT. There was a significantly higher IMH regression rate among patients undergoing TEVAR + BMT compared with BMT (odds ratios [OR] 10.0, 95% confidence interval [CI] 3.43-29.4). There were a significantly lower IMH progress rate and aortic-related death rate among patients undergoing TEVAR + BMT compared with BMT (OR 0.239, 95% CI 0.075-0.758; OR 0.248, 95% CI 0.085-0.725). When the study of Ye K et al. was excluded, the results showed no statistically significant differences.. Combined data from the present study demonstrate that TEVAR + BMT results in significantly higher IMH regression rate, lower IMH progression, and lower aortic-related death rate compared with BMT in high-risk type B IMH patients.

Topics: Adult; Aged; Aorta, Thoracic; Aortic Diseases; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Clinical Trials as Topic; Combined Modality Therapy; Endovascular Procedures; Female; Hematoma; Humans; Male; Middle Aged; Risk Factors; Treatment Outcome

Blunt abdominal aortic injury (BAAI) is a rare injury with less than 200 cases in the current reported world literature, mostly in case report format. We sought to describe the experience of a high-volume trauma center and to provide a contemporary review of the literature to better understand the natural history and management of this injury.. This was a retrospective review of patients with BAAI between 1996 and 2010. Data collected included demographics, mechanism of injury, associated injuries, type of intervention, subsequent imaging, and follow-up. BAAI was classified by the presence of external aortic contour abnormality noted as an intimal tear, large intimal flap, pseudoaneurysm, or free rupture. Abdominal aorta zones of injury were classified by possible surgical approaches as zone I (diaphragmatic hiatus to superior mesenteric artery [SMA]), zone II (includes SMA and renal arteries), and zone III (from the inferior aspect of the renal arteries to the aortic bifurcation).. We identified 28 individuals (68% male) with BAAI (median age, 28.5; range, 6-61 years). The median injury severity score was 45 (range, 16-75), and 39% were hypotensive at presentation. BAAI presented as intimal tear (21%), large intimal flap (39%), pseudoaneurysm (11%), and free rupture (29%). Zone III was the most common location of injury. Management depended on the location and type of injury: nonoperative (32%), open aortic repair (36%), endovascular repair (21%), and multimodality (10%). Overall mortality was 32%. Most deaths occurred during the initial operative exploration. The mortality rate of free aortic rupture was 100%. Intimal tears resolved or remained stable. Median follow-up was 15.5 months (range, 8 days-7.5 years). Vascular complications due to repair included a thrombosed access femoral artery during an endovascular repair and death of a patient who underwent a hybrid repair.. This is the largest BAAI series described in the English literature at one institution. BAAIs range from intimal tears to free rupture, with outcomes and management correlating with type and location of injury. Nonoperative management with blood pressure control using β-blockers coupled with antiplatelet therapy and close follow-up is successful in individuals with intimal tears with minimal thrombus formation because they remain stable or resolve on follow-up. Free rupture remains a devastating injury, with 100% mortality. For all other categories of aortic injury, successful repair correlates with a favorable prognosis.

Topics: Adolescent; Adult; Aneurysm, False; Aorta, Abdominal; Aortic Aneurysm; Aortic Diseases; Aortic Rupture; Aortography; Cardiovascular Agents; Child; Endovascular Procedures; Female; Humans; Incidence; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Severity of Illness Index; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Vascular Surgical Procedures; Vascular System Injuries; Washington; Wounds, Nonpenetrating; Young Adult

Stroke is the most debilitating cardiovascular event. It has a variety of causes that may be present simultaneously. In young or otherwise healthy people, the search for a patent foramen ovale (PFO) has become standard. In stroke of the elderly, atherosclerosis and atrial fibrillation are in the foreground but the PFO should not be ignored. The risk of a PFO-related stroke over time is controversial and so is its prevention by device closure. The association of proximal aortic plaques in arteries subtending the brain and stroke is considered strong, ignoring that it is as putative as that of the PFO. Statins can prevent progression of such plaques. Antiplatelet agents in asymptomatic and surgical endarterectomy in symptomatic patients or highly ulcerated lesions are the treatment of choice. Stenting with protection devices was shown competitive in selected patients.

Topics: Anticoagulants; Aortic Diseases; Balloon Occlusion; Cardiovascular Agents; Carotid Stenosis; Foramen Ovale, Patent; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Prosthesis Design; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Secondary Prevention; Septal Occluder Device; Stents; Stroke

In various cardiac diseases, thrombembolism constitutes a major risk, and in these patients clinically silent microembolic signals (MES) are detectable within the transcranial Doppler frequency spectrum (TCD) of the major brain arteries. MES are already an accepted surrogate parameter of the future risk of stroke in patients with carotid artery stenosis. The aim of this review is to summarize and evaluate the data about occurence and clinical impact of MES in patients with chronic cardiac diseases and to clarify whether cardiogenic MES can serve as a surrogate parameter of the heart's future thrombembolic risk as well.. We performed a systematic MEDLINE search and reviewed the currently available literature about chronic cardiac diseases and atheroaortic plaques leading to MES apart from cardiosurgical procedures.. The cardiac conditions producing MES are heterogenous and therefore the prevalence of MES is highly variable. The data in patients with acute or after myocardial infarction, endocarditis, patent foramen ovale, mitral valve prolapse, dilatative cardiomyopathy and intracardiac thrombus is promising but only small patient cohorts have been investigated by means of TCD in these categories. MES in atrial fibrillation, or derived from atheroaortic plaques, have been investigated more intensively, but again larger cohorts need to be explored to draw firm conclusions. In all cardiac diseases there is a lack of large prospective studies allowing to reliably correlating MES with clinical events. Compared to carotid artery disease, the current knowledge about the impact of cardiogenic MES on the patient's risk is sparse. This should encourage the clinical research in this promising field.

Topics: Aortic Diseases; Atherosclerosis; Cardiovascular Agents; Chronic Disease; Heart Diseases; Humans; Intracranial Embolism; Risk Factors; Ultrasonography, Doppler, Transcranial

The cardiovascular complications of Marfan syndrome (MFS) remain the primary source of morbidity and mortality in affected patients. Over the last decade, the underlying pathogenesis of these cardiovascular abnormalities has been the focus of much research. Such research has shed light on the potential role of several novel medical therapies and their ability to prevent cardiovascular disease progression. This paper summarizes the research underlying new medical therapies and provides a review of the scientific foundation underlying all current medical therapies used for prevention of cardiovascular disease in patients with MFS, including beta-adrenoceptor antagonists, calcium channel antagonists, ACE inhibitors, and angiotensin receptor antagonists.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Aortic Diseases; Calcium Channel Blockers; Cardiovascular Agents; Cardiovascular Diseases; Humans; Marfan Syndrome

Use of molecular tools to diagnose and treat aortic disease, in particular, aortic aneurysms and aortic dissections, is still in its infancy, with great advancements expected in the future. Currently under investigation are the genetic markers linked to aortic disease that may help to identify patients at risk for their development prior to clinical presentation. In addition, specific gene defects may be identified that can assist in the understanding of the basic mechanisms contributing to development of aortic disease. Biomarkers are under investigation that can be used to monitor the development, progression, and possible response to therapy for aortic aneurysms and acute aortic syndromes. Equally important, further investigations into the molecular mechanisms involved in aortic pathology will result in increased understanding of the disease etiology and will lead to development of alternate therapies for these diseases prior to their catastrophic development. With advances in molecular technology, the molecular diagnosis and treatment of aortic diseases will begin to expand at a rapid rate and provide unique, improved therapies.

Topics: Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Aortic Diseases; Aortic Dissection; Biomarkers; Cardiovascular Agents; Genetic Predisposition to Disease; Genetic Therapy; Humans; Molecular Diagnostic Techniques; Risk Factors; Signal Transduction; Syndrome

Both supervised exercise (SE) and stenting (ST) improve functional status, symptoms, and quality of life compared with optimal medical care (OMC) in patients with claudication. The relative cost-effectiveness of these strategies is not well defined.. The Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) study randomized patients with claudication due to aortoiliac stenosis to a 6-month SE program, to ST, or to OMC. Participants who completed 6-month follow-up (n=98) were included in a health economic analysis through 18 months. Costs were assessed using resource-based methods and hospital billing data. Quality-adjusted life-years were estimated using the EQ-5D. Markov modeling based on the in-trial results was used to explore the impact of assumptions about the longer term durability of observed differences in quality of life. Through 18 months, mean healthcare costs were $5178, $9804, and $14 590 per patient for OMC, SE, and ST, respectively. Measured quality-adjusted life-years through 18 months were 1.04, 1.16, and 1.20. In our base case analysis, which assumed that observed differences in quality of life would dissipate after 5 years, the incremental cost-effectiveness ratios were $24 070 per quality-adjusted life-year gained for SE versus OMC, $41 376 for ST versus OMC, and $122 600 for ST versus SE. If the treatment effect of ST was assumed to be more durable than that of SE, the incremental cost-effectiveness ratio for ST versus SE became more favorable.. Both SE and ST are economically attractive by US standards relative to OMC for the treatment of claudication in patients with aortoiliac disease. ST is more expensive than SE, with uncertain incremental benefit.. www.clinicaltrials.gov, Unique identifier: NCT00132743.

Topics: Ambulatory Care; Aortic Diseases; Cardiovascular Agents; Constriction, Pathologic; Cost-Benefit Analysis; Drug Costs; Endovascular Procedures; Exercise Therapy; Health Care Costs; Hospital Costs; Humans; Iliac Artery; Intermittent Claudication; Life Expectancy; Models, Economic; Peripheral Arterial Disease; Quality of Life; Quality-Adjusted Life Years; Stents; Time Factors; Treatment Outcome; United States; Vascular Patency

Topics: Aorta, Thoracic; Aortic Diseases; Cardiovascular Agents; Chest Pain; Computed Tomography Angiography; Conservative Treatment; Coronary Angiography; Diagnosis, Differential; Electrocardiography; Fibrin Fibrinogen Degradation Products; Hematoma; Humans; Male; Middle Aged; Nitroglycerin; Telmisartan; Treatment Outcome

Topics: Acute Coronary Syndrome; Acute Disease; Aortic Diseases; Cardiovascular Agents; Humans; Prognosis; Stents

This study aimed to investigate the effects and molecular mechanisms of ivabradine in preventing cardiac hypertrophy in an established transverse aortic constriction (TAC) mouse model. A total of 56 male C57BL/6 mice were randomly assigned into the following seven groups (8 mice per group): sham, TAC model, Iva-10 (10 mg/kg/day ivabradine), Iva-20 (20 mg/kg/day ivabradine), Iva-40 (40 mg/kg/day ivabradine), Iva-80 (80 mg/kg/day ivabradine), and Rap (rapamycin, a positive control). Echocardiography and left ventricular hemodynamics were performed. Hematoxylin-eosin (H&E), Masson's trichome staining, and TUNEL assays were conducted to evaluate cardiac hypertrophy, fibrosis, and apoptosis, respectively. Western blotting was performed to detect the expression of proteins related to the PI3K/Akt/mTOR/p70S6K pathway. Ivabradine could effectively improve left ventricular dysfunction and hypertrophy induced by TAC in a dose-independent manner. Moreover, no obvious change in heart rate (HR) was observed in the TAC and Rap groups, whereas a significant decrease in HR was found after ivabradine treatment (P < 0.05). Cardiac hypertrophy, fibrosis, and apoptosis induced by TAC were notably suppressed after either rapamycin or ivabradine treatment (P < 0.05). Ivabradine and rapamycin also decreased the expression of PI3K/Akt and mTOR induced by TAC. Ivabradine improved cardiac hypertrophy and fibrosis as well as reduced cardiomyocyte apoptosis via the PI3K/Akt/mTOR/p70S6K pathway in TAC model mice.

Topics: Animals; Aortic Diseases; Apoptosis; Cardiovascular Agents; Constriction, Pathologic; Disease Models, Animal; Hypertrophy, Left Ventricular; Ivabradine; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Pressure; Ventricular Dysfunction, Left

Hypomagnesemia was identified as a strong risk factor for cardiovascular disease in patients with chronic renal failure (CRF). However, the effects of magnesium (Mg) on vascular calcification (VC) have not been fully elucidated. Thus, we aim to determine the effects of Mg citrate (MgCit) on VC in CRF rats.. Rats were divided into 5 groups: group 1 (normal diet), group 2 (normal diet with MgCit), group 3 (the VC model of CRF induced by 0.75% adenine and 0.9% phosphorus diet from day 1 to day 28), group 4 (group 3 treated with low-dose MgCit from day 1 to day 42), and group 5 (same as group 3 except the high-dose MgCit). All rats were killed at day 43 with collection of blood and aortas. Then, serum biochemical parameters, VC-related staining, calcium and P contents, alkaline phosphatase contents and activity, expression of alpha smooth muscle actin, and runt-related transcription factor 2 (RUNX2) in aortas were assessed.. Group 3 had extensive VC. The VC degree decreased in groups 4 and 5 in a dose-depended manner with reduced calcium content, P levels, alkaline phosphatase content and activity, and protein levels of RUNX2 and increased protein levels of alpha smooth muscle actin in aortas.. MgCit exerted a protective role in VC in adenine-induced CRF rats; thus, it may be a potential drug for the prevention of VC in patients with CRF.

Topics: Actins; Adenine; Alkaline Phosphatase; Animals; Aorta; Aortic Diseases; Calcium; Cardiovascular Agents; Citric Acid; Core Binding Factor Alpha 1 Subunit; Disease Models, Animal; Kidney Failure, Chronic; Male; Organometallic Compounds; Phosphorus, Dietary; Rats, Sprague-Dawley; Vascular Calcification

In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding. Thirty-eight rabbits were fed 1% cholesterol chow for 8 weeks. Six of these rabbits were then euthanized for analyses of the aorta (controls). In the remaining rabbits, cholesterol feeding was withdrawn, and those 32 animals were allocated to 3 groups submitted to different 8-week intravenous treatments, all once/week: LDE-PTX (n = 10; 4 mg/kg), LDE-PTX + LDE-MTX (n = 11; 4 mg/kg), and LDE-alone (n = 11). Rabbits were then euthanized and aortas were excised for morphometric, immunohistochemical, and gene expression analyses. After cholesterol feeding withdrawal, in comparison with LDE-alone group, both LDE-PTX and LDE-PTX + LDE-MTX treatments had the ability to increase the regression of plaque areas: -49% in LDE-PTX and -59% for LDE-PTX + LDE-MTX. However, only LDE-PTX + LDE-MTX treatment elicited reduction in the intima area, estimated in -57%. Macrophage presence in aortic lesions was reduced 48% by LDE-PTX and 43% by LDE-PTX + LDE-MTX treatment. Matrix metalloproteinase 9 was reduced by either LDE-PTX (74%) or LDE-PTX + LDE-MTX (78%). Tumor necrosis factor α gene expression was reduced 65% by LDE-PTX and 79% by LDE-PTX + LDE-MTX. In conclusion, treatment with LDE-PTX indeed accelerated plaque reduction after cholesterol feeding; LDE-PTX + LDE-MTX further increased this effect, without any observed toxicity. These results pave the way for the use of combined chemotherapy to achieve stronger effects on aggravated, highly inflamed atherosclerotic lesions.

Topics: Animals; Aorta; Aortic Diseases; Atherosclerosis; Cardiovascular Agents; Cholesterol, Dietary; Cytokines; Disease Models, Animal; Drug Compounding; Drug Therapy, Combination; Inflammation Mediators; Lipids; Liposomes; Male; Matrix Metalloproteinase 9; Methotrexate; Nanoparticles; Paclitaxel; Plaque, Atherosclerotic; Rabbits

Heart failure is a common, costly, and potentially fatal condition. The cardiac sarcoplasmic reticulum Ca-ATPase (SERCA2a) plays a critical role in the regulation of cardiac function. Previously, low SERCA2a expression was revealed in mice with heart failure. Epigallocatechin-3-gallate (EGCG) can function as an epigenetic regulator and has been reported to enhance cardiac function. However, the underlying epigenetic regulatory mechanism is still unclear. In this study, we investigated whether EGCG can up-regulate SERCA2a via histone acetylation and play role in preventing heart failure. For this, we generated a mouse model of heart failure by performing a minimally invasive transverse aortic constriction (TAC) operation and used this to test the effects of EGCG. The TAC+EGCG group showed nearly normal cardiac function compared to that in the SHAM group. The expression of SERCA2a was decreased at both the mRNA and protein levels in the TAC group but was enhanced in the TAC+EGCG group. Levels of AcH3 and AcH3K9 were determined to decrease near the promoter region of Atp2a2 (the gene encoding SERCA-2a) in the TAC group, but were elevated in the TAC+EGCG group. Meanwhile, HDAC1 activity and binding near the Atp2a2 promoter were increased in the TAC group but decreased with EGCG addition. Further, binding levels of GATA4 and Mef2c near the Atp2a2 promoter region were reduced in TAC hearts, which might have been caused by histone hypoacetylation; this was reversed by EGCG. Together, upregulation of SERCA2a via the modification of histone acetylation plays a role in EGCG-mediated prevention of pressure overload-induced heart failure, and this might represent a novel pharmacological target for the treatment of heart failure.

Topics: Acetylation; Animals; Aortic Diseases; Cardiovascular Agents; Catechin; Constriction, Pathologic; Disease Models, Animal; Heart Failure; Histone Deacetylase 1; Histones; Male; Mice, Inbred C57BL; Promoter Regions, Genetic; Protective Agents; Random Allocation; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Up-Regulation

Topics: Aortic Diseases; Cardiovascular Agents; Carotid Artery Diseases; Humans; Leg; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Stents; Venous Thromboembolism

Apple polyphenol contains abundant procyanidins, which have been associated with an anti-atherosclerosis and cholesterol-lowering effect. The aim of this study was to investigate whether apple procyanidins (APCs) feature therapeutic efficacy in terms of regressing atherosclerosis and whether this efficacy is due to mechanisms other than a cholesterol-lowering effect.. After eight weeks on an atherogenic diet, rabbits were given a normal diet for another eight weeks to normalize the increased serum lipids level. The rabbits in the baseline group were sacrificed at this stage. The control group was subsequently fed a normal diet for eight weeks, while the APCs group was administrated 50 mg/kg/day of APCs in addition to the normal diet. Serum lipids and aortic intimal-medial thickness (IMT) were serially examined, and the resected aorta was examined histologically and through molecular biology.. Aortic IMT on ultrasonography and the lipid accumulation area examined using Sudan IV staining were significantly reduced in the APCs group as compared to the control group. Serum lipid profiles were not different between the groups. Immunohistochemistry showed significantly decreased staining of an oxidative stress marker and significantly increased staining of ATP-binding cassette subfamily A member 1 (ABCA1) in the APCs group. Western blotting and RT-PCR also showed increased expression of ABCA1 mRNA and its protein in the APCs group.. This study revealed that APCs administration causes a regression of atherosclerosis. APCs might hold promise as an anti-atherosclerotic agent.

Topics: Animals; Aorta; Aortic Diseases; Atherosclerosis; ATP Binding Cassette Transporter 1; Biflavonoids; Cardiovascular Agents; Catechin; Cholesterol; Disease Models, Animal; Fruit; Lipoproteins, LDL; Male; Malus; Oxidative Stress; Phytotherapy; Plants, Medicinal; Plaque, Atherosclerotic; Proanthocyanidins; Reactive Oxygen Species; RNA, Messenger; Scavenger Receptors, Class E; Time Factors; Up-Regulation

Buchang NaoXinTong (NXT), a Chinese medicine, has been widely used to treat patients with coronary heart disease in China. However, the underlying mechanisms need more elucidations. In this study, we investigated if NXT can inhibit the progression of the established lesions while stabilizing plaques. Apolipoprotein E deficient (apoE(-/-)) mice in 3 groups received following treatment: group 1 was fed a high-fat diet (HFD) for 18 weeks; group 2 was prefed HFD for 12 weeks followed by HFD containing NXT for additional 6 weeks; group 3 was prefed HFD for 8 weeks followed by HFD containing NXT for additional 10 weeks. After treatment, serum and aorta samples were collected and determined lipid profiles, lesions, collagen content, mineralization, and macrophage accumulation in aortic root, respectively. NXT had slight effect on serum lipid profiles but significantly reduced progression of the advanced lesions. In aortic wall, NXT increased smooth muscle cell/collagen content in lesion cap while reducing buried fibrous caps, mineralization, and macrophage accumulation within lesions, which suggests that NXT can stabilize plaques. In addition, NXT increased expression of smooth muscle 22α mRNA while inhibiting expression of matrix metalloproteinase-2 and tumor necrosis factor α mRNA in aortas. Our study demonstrates that NXT can reduce advanced atherosclerosis and enhance the plaque stability in apoE(-/-) mice.

Topics: Actins; Animals; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Biomarkers; Cardiovascular Agents; Diet, High-Fat; Disease Models, Animal; Drugs, Chinese Herbal; Fibrosis; Gene Expression Regulation; Genetic Predisposition to Disease; Lipids; Macrophages; Male; Matrix Metalloproteinase 2; Mice, Knockout; Phenotype; Phytotherapy; Plants, Medicinal; Plaque, Atherosclerotic; RNA, Messenger; Rupture, Spontaneous; Time Factors; Tumor Necrosis Factor-alpha

Aortic mural thrombi in a normal (non-aneurysmal or minimally atherosclerotic) vessel are an uncommon condition. They are usually located in the descending aorta and, less frequently, in the aortic arch or in the abdominal aorta. The typical clinical presentation is the appearance of symptoms/signs of peripheral arterial embolization, such as lower limb or visceral ischaemia, but these can also be accidentally found in asymptomatic patients. We report the case of a 40-year old man with untreated hypertension and dyslipidaemia admitted to hospital for atypical chest pain associated with an elevation in high-sensitivity troponin T with normal creatine kinase isoenzime MB creatine kinase isoenzyme. Elektrocardiogram (EKG) and transthoracic echocardiography were non-diagnostic; in order to exclude an aortic dissection, a gated chest computed tomography was performed and showed an aortic thrombus on a minimally atherosclerotic wall. Then, a transoesophageal echocardiography confirmed an aortic floating thrombus (7 × 4 mm). Cardiac surgeons advised against surgery and therapy with antiplatelet, low molecular weight heparin, β-blocker, antihypertensive and lipid-lowering drugs was initiated. A complete resolution of the thrombus was observed at the 12-day tomographic control.

Topics: Adult; Aorta, Thoracic; Aortic Diseases; Aortography; Asymptomatic Diseases; Atherosclerosis; Cardiovascular Agents; Echocardiography, Transesophageal; Humans; Male; Plaque, Atherosclerotic; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome

Drug-eluting coronary stents reduce restenosis rate and late lumen loss compared with bare-metal stents; however, drug-eluting coronary stents may delay vascular healing and increase late stent thrombosis. The peroxisome proliferator-activated receptor-delta (PPARδ) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement.. Here, we report that PPARδ ligand-coated stents strongly reduce the development of neointima and luminal narrowing in a rabbit model of experimental atherosclerosis. Inhibition of inflammatory gene expression and vascular smooth muscle cell (VSMC) proliferation and migration, prevention of thrombocyte activation and aggregation, and proproliferative effects on endothelial cells were identified as key mechanisms for the prevention of restenosis. Using normal and PPARδ-depleted VSMCs, we show that the observed effects of PPARδ ligand GW0742 on VSMCs and thrombocytes are PPARδ receptor dependent. PPARδ ligand treatment induces expression of pyruvate dehydrogenase kinase isozyme 4 and downregulates the glucose transporter 1 in VSMCs, thus impairing the ability of VSMCs to provide the increased energy demands required for growth factor-stimulated proliferation and migration.. In contrast to commonly used drugs for stent coating, PPARδ ligands not only inhibit inflammatory response and proliferation of VSMCs but also prevent thrombocyte activation and support vessel re-endothelialization. Thus, pharmacological PPARδ activation could be a promising novel strategy to improve drug-eluting coronary stents outcomes.

Topics: Angioplasty, Balloon; Animals; Aorta; Aortic Diseases; Atherosclerosis; Blood Platelets; Cardiovascular Agents; Carotid Artery Injuries; Cell Movement; Cell Proliferation; Cells, Cultured; Coronary Artery Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Eluting Stents; Energy Metabolism; Glucose Transporter Type 1; Human Umbilical Vein Endothelial Cells; Humans; Mice, Knockout; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Platelet Activation; PPAR delta; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Rats; Rats, Sprague-Dawley; Re-Epithelialization; Recurrence; Signal Transduction; Steroids; Thrombosis; Time Factors; Transfection

Blood vessel endothelial dysfunction induced by oxidized low-density lipoprotein (ox-LDL) has been implicated in the pathogenesis of atherosclerosis and vasculopathy. The ox-LDL-elicited reactive oxygen species (ROS) release has been assumed to serve a critical function in endothelial damage. Myricitrin (from Myrica cerifera) is a natural antioxidant that has strong anti-oxidative, anti-inflammatory, and anti-nociceptive activities. However, the protective effect of myricitrin on ROS-induced endothelial cell injury and its related molecular mechanisms have never been investigated. This study demonstrates that myricitrin can inhibit ox-LDL-induced endothelial apoptosis and prevent plaque formation at an early stage in an atherosclerotic mouse model. The administration of myricitrin in vivo decreases the thickness of the vascular wall in the aortic arch of ApoE-/- mice. In vitro study shows that ox-LDL-induced human umbilical vein endothelial cell apoptosis can be reduced upon receiving myricitrin pre-treatment. Treatment with myricitrin significantly attenuated ox-LDL-induced endothelial cell apoptosis by inhibiting LOX-1 expression and by increasing the activation of the STAT3 and PI3K/Akt/eNOS signaling pathways. At the same time, our result demonstrates that myricitrin treatment optimizes the balance of pro/anti-apoptosis proteins, including Bax, Bad, XIAP, cIAP-2, and survivin. Our study suggests that myricitrin treatment can effectively protect cells from ox-LDL-induced endothelial cell apoptosis, which results in reduced atherosclerotic plaque formation. This result indicates that myricitrin can be used as a drug candidate for the treatment of cardiovascular diseases.

Topics: Animals; Aortic Diseases; Apolipoproteins E; Apoptosis; Apoptosis Regulatory Proteins; Atherosclerosis; Biopsy; Cardiovascular Agents; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Activation; Flavonoids; Human Umbilical Vein Endothelial Cells; Humans; Lipoproteins, LDL; Male; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase Type III; Phosphatidylinositol 3-Kinase; Plaque, Atherosclerotic; Proto-Oncogene Proteins c-akt; Scavenger Receptors, Class E; Signal Transduction; STAT3 Transcription Factor; Time Factors; X-Ray Microtomography

Topics: Acute Disease; Age Factors; Aneurysm, False; Aorta, Abdominal; Aorta, Thoracic; Aortic Diseases; Aortic Dissection; Aortic Valve; Atherosclerosis; Bicuspid Aortic Valve Disease; Cardiovascular Agents; Clinical Laboratory Techniques; Diagnostic Imaging; Early Diagnosis; Endovascular Procedures; Female; Genetic Diseases, Inborn; Heart Defects, Congenital; Heart Valve Diseases; Hematoma; Humans; Long-Term Care; Male; Neoplasms, Vascular Tissue; Physical Examination; Risk Factors; Vascular Calcification; Vascular Stiffness; Vascular Surgical Procedures

Topics: Aorta; Aortic Diseases; Cardiovascular Agents; Diagnostic Techniques, Cardiovascular; Endovascular Procedures; Europe; Humans; Practice Guidelines as Topic; Societies, Medical; Vascular Surgical Procedures

Clinical studies show that metformin attenuates all‐cause mortality and myocardial infarction compared with other medications for type 2 diabetes, even at similar glycemic levels. However, there is paucity of data in the euglycemic state on the vasculoprotective effects of metformin. The objectives of this study are to evaluate the effects of metformin on ameliorating atherosclerosis.. Using ApoE−/− C57BL/6J mice, we found that metformin attenuates atherosclerosis and vascular senescence in mice fed a high‐fat diet and prevents the upregulation of angiotensin II type 1 receptor by a high‐fat diet in the aortas of mice. Thus, considering the known deleterious effects of angiotensin II mediated by angiotensin II type 1 receptor, the vascular benefits of metformin may be mediated, at least in part, by angiotensin II type 1 receptor downregulation. Moreover, we found that metformin can cause weight loss without hypoglycemia. We also found that metformin increases the antioxidant superoxide dismutase‐1.. Pleiotropic effects of metformin ameliorate atherosclerosis and vascular senescence.

Topics: Animals; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Blood Glucose; Cardiovascular Agents; Cellular Senescence; Disease Models, Animal; Hypoglycemic Agents; Male; Metformin; Mice, Inbred C57BL; Mice, Knockout; Receptor, Angiotensin, Type 1; Superoxide Dismutase; Superoxide Dismutase-1; Weight Loss

Topics: Adult; Aorta, Abdominal; Aortic Diseases; Aortography; Arterial Occlusive Diseases; Cardiovascular Agents; Chronic Disease; Collateral Circulation; Female; Humans; Middle Aged; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Walking

Sphingosine 1-phosphate (S1P) partly accounts for antiatherogenic properties of high-density lipoproteins. We previously demonstrated that FTY720, a synthetic S1P analog targeting all S1P receptors but S1P receptor type 2, inhibits murine atherosclerosis. Here, we addressed the identity of S1P receptor mediating atheroprotective effects of S1P.. Low-density lipoprotein receptor-deficient mice on cholesterol-rich diet were given selective S1P receptor type 1 agonist KRP-203 (3.0 mg/kg per day; 6 and 16 weeks). KRP-203 substantially reduced atherosclerotic lesion formation without affecting plasma lipid concentrations. However, KRP-203 induced lymphopenia, reduced total (CD4(+), CD8(+)) and activated (CD69(+)/CD8(+), CD69(+)/CD4(+)) T cells in peripheral lymphoid organs, and interfered with lymphocyte function, as evidenced by decreased T-cell proliferation and interleukin-2 and interferon-γ production in activated splenocytes. Cyto- and chemokine (tumor necrosis factor-α, regulated and normal T cell expressed and secreted) levels in plasma and aortas were reduced by KRP-203 administration. Moreover, macrophages from KRP-203-treated mice showed reduced expression of activation marker MCH-II and poly(I:C)-elicited production of tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-6. In vitro studies demonstrated that KRP-203 reduced tumor necrosis factor-α, interleukin-6, and interferon-γ-induced protein-10 production; IκB and signal transducer and activator of transcription-1 phosphorylation; and nuclear factor κB and signal transducer and activator of transcription-1 activation in poly(I:C)-, lipopolysaccharide-, or interferon-γ-stimulated bone marrow macrophages, respectively.. Present results demonstrate that activation of S1P signaling pathways inhibit atherosclerosis by modulating lymphocyte and macrophage function and suggest that S1P receptor type 1 at least partially mediates antiatherogenic effects of S1P.

Topics: Animals; Aorta; Aortic Diseases; Atherosclerosis; Biomarkers; Cardiovascular Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Dendritic Cells; Disease Models, Animal; Endothelial Cells; Humans; Inflammation; Inflammation Mediators; Lipids; Lymphocyte Activation; Lymphopenia; Macrophage Activation; Macrophages; Mice; Mice, Knockout; Receptors, LDL; Receptors, Lysosphingolipid; Signal Transduction; Sulfhydryl Compounds; U937 Cells

Topics: Acute Coronary Syndrome; Aged, 80 and over; Aortic Diseases; Atherosclerosis; Calcinosis; Cardiovascular Agents; Colitis, Ischemic; Dietary Supplements; Humans; Hyperparathyroidism, Secondary; Hypertension; Hypotension; Kidney Failure, Chronic; Male; Myocardial Ischemia; Nephrosclerosis; Obesity; Parenteral Nutrition; Pneumatosis Cystoides Intestinalis; Renal Dialysis; Splanchnic Circulation

Recent studies indicate that regulatory T cells (Tregs) attenuate murine atherosclerosis. Since interleukin (IL)-2 induces Tregs proliferation, we tested the impact of L19-IL2, a fusion antibody specific to extra-domain B of fibronectin (ED-B) containing an active human IL-2 molecule, in experimental atherosclerosis.. L19-IL2 or appropriate controls were given intravenously to 6 month old Western diet-fed apoE(-/-) mice on day 1, 3, and 5. Human IL-2 was detected on day 7 within atherosclerotic plaques of L19-IL2-treated mice, and magnetic resonance imaging of the plaques showed a significant adventitial gadolinium enhancement on day 7 and 13, suggesting microvascular leakage as a result of the pharmacodynamic activity of L19-IL2. Treatment with L19-IL2 significantly reduced the size of pre-established atherosclerotic plaques at the thoracic aorta (Sudan III stained area) and in the aortic root area (microscopic, morphometric analysis) on day 7 as compared to controls (L19, D1.3-IL2, NaCl) as well as compared to baseline (day 0). Tregs markers Foxp3 and CTLA4 were highly increased in plaques after L19-IL2 treatment compared to controls (p<0.01), whereas the macrophage marker Mac3 was significantly reduced (p<0.03). Co-treatment with IL-2-receptor blocking antibody PC61 abrogated L19-IL2-induced plaque reduction compared with IgG control (p<0.03).. L19-IL2 delivers functional IL-2 to pre-established atherosclerotic plaques of WD-fed apoE(-/-) mice resulting in significant plaque size reduction mediated by local Tregs.

Topics: Animals; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Cardiovascular Agents; Cell Proliferation; Diet, High-Fat; Disease Models, Animal; Humans; Injections, Intravenous; Lipids; Macrophages; Magnetic Resonance Imaging; Mice; Mice, Inbred C57BL; Mice, Knockout; Recombinant Fusion Proteins; T-Lymphocytes, Regulatory; Time Factors

This study evaluated the effect of prostaglandin E1 (PGE1) on the stability of atherosclerotic plaque. A vulnerable plaque model was established in rabbits, using balloon injury combined with a high-cholesterol diet. The rabbits were distributed into a control group, a low-dose PGE1 treatment group, a moderate-dose PGE1 treatment group, a high-dose PGE1 treatment group, and a simvastatin treatment group, with treatments lasting for 4 weeks. At week 13 (at the end of the experiments), atherosclerotic plaque was triggered by injection of Russell's viper venom (Chinese) and histamine. Serological, pathological, immunohistochemical, and gene-expression studies were subsequently performed. PGE1 treatment did not alter serum lipid levels; however, PGE1 dose-dependently increased the thickness of the fibrous caps, and decreased the plaque vulnerability index. The plaque contents of macrophage- and the mRNA levels of monocyte-chemotactic protein-1, matrix metalloproteinase-1, and matrix metalloproteinase-9 were markedly reduced in all of the PGE1 treatment groups, with the high-dose of PGE1 being more effective than the simvastatin treatment. These findings suggest that PGE1 dose-dependently enhances the stability of atherosclerotic plaque. The high-dose of PGE1 presented more protection in terms of inhibiting macrophage accumulation and inflammatory expression in plaque. Our findings suggest a novel drug for the treatment of atherosclerosis.

Topics: Alprostadil; Angioplasty, Balloon; Animals; Anti-Inflammatory Agents; Aorta, Abdominal; Aortic Diseases; Atherosclerosis; Cardiovascular Agents; Chemokine CCL2; Cholesterol, Dietary; Cytokines; Daboia; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Down-Regulation; Fibrosis; Histamine; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation Mediators; Lipid Metabolism; Macrophages; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 9; Plaque, Atherosclerotic; Rabbits; RNA, Messenger; Simvastatin; Viper Venoms

Topics: Aorta, Abdominal; Aortic Diseases; Cardiovascular Agents; Endovascular Procedures; Female; Humans; Male; Vascular Surgical Procedures; Vascular System Injuries; Wounds, Nonpenetrating

Topics: Aorta, Abdominal; Aortic Diseases; Cardiovascular Agents; Endovascular Procedures; Female; Humans; Male; Vascular Surgical Procedures; Vascular System Injuries; Wounds, Nonpenetrating

The Impact of Nicorandil in Angina (IONA) trial demonstrated that the use of nicorandil, an anti-anginal drug, reduced future cardiovascular events in patients with stable angina. We hypothesized that nicorandil has beneficial effects on coronary arterial plaque characteristics and atherosclerogenesis.. Preintervention intravascular ultrasound-virtual histology was performed prospectively in 65 consecutive patients with stable angina pectoris. There were no differences in coronary risk factors between the nicorandil (n = 16) and non-nicorandil (n = 49) groups. However, the nicorandil group demonstrated a larger %fibrous tissue (68 ± 10 vs. 62 ± 11%, P = 0.049) and a smaller %necrotic core tissue (11 ± 7 vs. 16 ± 10%, P = 0.049) compared with the non-nicorandil group. Multiple regression analysis showed that %necrotic core tissue (P = 0.045) was negatively and %fibrous tissue (P = 0.026) was positively associated with the use of nicorandil independent of statin use. We also analyzed the effect of nicorandil on atherosclerotic lesion formation in a mouse model of atherosclerosis. Lipid profiles were unaffected, but the area of atherosclerotic lesion and plaque necrosis were significantly reduced following 8-week nicorandil treatment in ApoE-deficient mice fed an atherogenic diet. Nicorandil significantly reduced the expression levels of endoplasmic reticulum stress markers, C/EBP homologous protein (CHOP) and glucose regulated protein/BiP (GRP78) in atherosclerotic lesions. Nicorandil significantly attenuated tunicamycin-induced CHOP upregulation in cultured THP-1 macrophages.. Nicorandil exerts its anti-atherogenic effect by mechanisms different from those of statins. Long-term nicorandil treatment is a potentially suitable second-line prevention therapy for patients with coronary artery disease.

Topics: Administration, Oral; Aged; Aged, 80 and over; Angina Pectoris; Animals; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Cardiovascular Agents; Cells, Cultured; Chi-Square Distribution; Coronary Artery Disease; Cytokines; Disease Models, Animal; Drug Administration Schedule; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Endothelial Cells; Fibrosis; Humans; Inflammation Mediators; Japan; Lipids; Logistic Models; Macrophages; Male; Mice; Mice, Knockout; Middle Aged; Molecular Chaperones; Necrosis; Nicorandil; Odds Ratio; Retrospective Studies; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Sesamol, a phenolic component of lignans, has been previously shown to reduce lipopolysaccharide-induced oxidative stress and upregulate phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase pathways. In the present study, we synthesized a modified form of sesamol (INV-403) to enhance its properties and assessed its effects on atherosclerosis.. Watanabe heritable hyperlipidemic rabbits were fed with high-cholesterol chow for 6 weeks and then randomized to receive high-cholesterol diet either alone or combined with INV-403 (20 mg/kg per day) for 12 weeks. Serial MRI analysis demonstrated that INV-403 rapidly reduced atherosclerotic plaques (within 6 weeks), with confirmatory morphological analysis at 12 weeks posttreatment revealing reduced atherosclerosis paralleled by reduction in lipid and inflammatory cell content. Consistent with its effect on atherosclerosis, INV-403 improved vascular function (decreased constriction to angiotensin II and increased relaxation to acetylcholine), reduced systemic and plaque oxidative stress, and inhibited nuclear factor-κB activation via effects on nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation with coordinate reduction in key endothelial adhesion molecules. In vitro experiments in cultured endothelial cells revealed effects of INV-403 in reducing IκBα phosphorylation via inhibition of IκB kinase 2 (IKK2).. INV-403 is a novel modified lignan derivative that potently inhibits atherosclerosis progression via its effects on IKK2 and nuclear factor-κB signaling.

Topics: Animals; Aorta; Aortic Diseases; Atherosclerosis; Benzodioxoles; Cardiovascular Agents; Cattle; Cell Adhesion Molecules; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelial Cells; Gene Expression Regulation; Hyperlipidemias; I-kappa B Kinase; I-kappa B Proteins; Magnetic Resonance Imaging; Male; NF-kappa B; NF-KappaB Inhibitor alpha; Oxidative Stress; Phenols; Phosphorylation; Rabbits; Time Factors; Transfection; Vasoconstriction; Vasodilation

The peroxisome proliferator-activated receptor-γ (PPARγ) agonist rosiglitazone has been suggested to exert cardiovascular protection through the improvement of lipid metabolism, anti-inflammation, anti-proliferation etc. However, whether renin-angiotensin system (RAS) is involved in the vascular protective effects of PPARγ agonists is not fully understood. The present study aimed to investigate the effects of the renin-angiotensin system in vascular protection mediated by PPARγ agonists.. To investigate the actions of the renin-angiotensin system in vascular protection mediated by activation of PPARγ in vivo and in vitro.. Rats were fed a regular diet (n = 8), a cholesterol-rich diet plus methylthiouracil (80 mg/Kg/day, n = 10), a cholesterol-rich diet plus methylthiouracil and rosiglitazone (4 mg/kg/day, n = 10). The rosiglitazone treatment was started from one month after the start of cholesterol-rich diet plus methylthiouracil, and lasted five months. Cultured vascular smooth muscle cells (VSMCs) were pretreated with 1 μmol/L angiotensin II (ANG II) for 6 h and randomly divided into the control group; the ANG II group (1 μmol/L ANG II); the groups respectively treated with different concentration rosiglitazone (20, 30, 50) μmol/L for 12 h; the groups treated with 30 μmol/L rosiglitazone for (6, 12, 24) h. Morphology changes of the aortic tissues were observed by hematoxylin and eosin stain. The VSMC growth was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Angiotensin II and expression of angiotensin receptors were determined by radioimmunoassay, reverse transcription polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry.. After 6 months, lipid deposition, VSMC proliferation and migration toward intima were observed in aortic tissues in the rats on a cholesterol-rich diet plus methylthiouracil, while these pathological changes induced by the cholesterol-rich diet were significantly suppressed by rosiglitazone. In addition, VSMC proliferation induced by ANG II was markedly inhibited by rosiglitazone. Rosiglitazone markedly down-regulated expression of angiotensin type 1 receptor (AT1R) and up-regulated expression of angiotensin type 2 receptor (AT2R) in the aortic tissues and ANG II-treated VSMCs.. The present study demonstrated that PPARγ agonist rosiglitazone suppressed ANG II-induced VSMC proliferation in vitro and early atherosclerotic formation evoked by cholesterol-rich diet in vivo. These vasculoprotective effects of rosiglitazone were mediated at least partially by reduction in local tissue ANG II concentration, down-regulation of AT1R expression and up-regulation of AT2R expression both at the mRNA and protein levels.

Topics: Angiotensin II; Animals; Aortic Diseases; Atherosclerosis; Blotting, Western; Cardiovascular Agents; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Hypercholesterolemia; Immunohistochemistry; Lipids; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; PPAR gamma; Radioimmunoassay; Rats; Rats, Inbred WKY; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Rosiglitazone; Thiazolidinediones; Time Factors

Although recent studies suggest that medical treatment is appropriate for patients with aortic intramural hematoma (IMH), the outcomes of supportive medical treatment alone have not been satisfactory, and clear guidelines for medical treatment are not yet available. We assessed whether a management protocol of combined early aggressive medical treatment and selective prophylactic aortic stent-grafting would benefit patients with IMH.. Nineteen patients with IMH were prospectively studied; after initial clinical and radiological evaluation, 13 underwent early aggressive medical therapy (group 1), and 6 underwent early aggressive medical therapy and prophylactic endovascular stent-grafting (group 2).. In group 1, one patient with type A IMH died prior to surgical consultation because of cardiac tamponade; another patient with type A IMH underwent replacement of the ascending aorta at the 6-month follow-up. The condition of the other 11 patients stabilized during hospitalization and after discharge. The disease spontaneously regressed in 10 patients, and the intramural hematoma completely resolved in 5 patients. In group 2, follow-up imaging revealed complete coverage of the penetrating aortic ulcers and regression of the intramural hematoma; endovascular leaks have not yet occurred.. Our protocol may be used as an alternative approach for patients with IMH. After initial clinical and radiological evaluation, the condition of patients without complications can be stabilized with medical treatment; frequent follow-up imaging is required in such cases. Early aggressive medical treatment combined with prophylactic aortic stent-grafting is a safe and effective treatment modality for IMH patients with penetrating aortic ulcers in the descending aorta.

Topics: Aged; Aortic Diseases; Aortography; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; China; Combined Modality Therapy; Drug Therapy, Combination; Endovascular Procedures; Female; Hematoma; Humans; Male; Middle Aged; Prospective Studies; Stents; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Ulcer

To determine the efficacy of sirolimus-eluting bioabsorbable magnesium alloy stents (SEBMAS) in restenosis prevention.. A balloon-expandable bioabsorbable magnesium alloy stent (BMAS) was created and coated with biodegradable poly(lactic acid-co-trimethylene carbonate) that contained the antiproliferative drug sirolimus (140 ± 40 µg/cm²). Both the uncoated BMAS and the coated SEBMAS were deployed 2 cm apart in balloon-injured infrarenal abdominal aortas of 20 New Zealand white rabbits. The stented aortic segments were removed at 30, 60, 90, and 120 days (5 rabbits per interval) after implantation. The average stent strut sectional area of each group was measured to evaluate the degree of magnesium corrosion and to forecast the biodegradation time profile of the magnesium stent. Histology and histopathology of the sectioned stented aortic segments were performed to evaluate neointima formation, endothelialization, and inflammation.. The SEBMAS degraded gradually after being implanted into the rabbit aorta, and total biocorrosion occurred after ~120 days. In all groups, the lumen area was significantly greater, but the neointimal area was significantly smaller in SEBMAS segments compared with the uncoated BMAS segments (p < 0.05) at all time points. There was no significant difference in the injury or inflammation scores between the groups. Endothelialization was delayed at 30 days in the SEBMAS segments vs. the uncoated BMAS segments.. SEBMAS further reduces intimal hyperplasia and improves the lumen area when compared to uncoated BMAS; however, it delays vascular healing and endothelialization.

Topics: Alloys; Angioplasty; Animals; Aorta, Abdominal; Aortic Diseases; Arterial Occlusive Diseases; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Constriction, Pathologic; Dioxanes; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells; Hyperplasia; Lactic Acid; Magnesium; Male; Polyesters; Polymers; Prosthesis Design; Rabbits; Secondary Prevention; Sirolimus; Time Factors; Wound Healing

Topics: Alloys; Angioplasty; Animals; Aorta, Abdominal; Aortic Diseases; Arterial Occlusive Diseases; Cardiovascular Agents; Coated Materials, Biocompatible; Drug-Eluting Stents; Magnesium; Male; Sirolimus

Accelerated atherosclerosis is a major diabetic complication initiated by the enhanced recruitment of monocytes into the vasculature. In this study, we examined the therapeutic potential of the phytonutrients ursolic acid (UA) and resveratrol (RES) in preventing monocyte recruitment and accelerated atherosclerosis.. Dietary supplementation with either RES or UA (0.2%) protected against accelerated atherosclerosis induced by streptozotocin in high-fat diet-fed LDL receptor-deficient mice. However, mice that received dietary UA for 11 weeks were significantly better protected and showed a 53% reduction in lesion formation while mice fed a RES-supplemented diet showed only a 31% reduction in lesion size. Importantly, UA was also significantly more effective in preventing the appearance of proinflammatory GR-1(high) monocytes induced by these diabetic conditions and reducing monocyte recruitment into MCP-1-loaded Matrigel plugs implanted into these diabetic mice. Oxidatively stressed THP-1 monocytes mimicked the behavior of blood monocytes in diabetic mice and showed enhanced responsiveness to monocyte chemoattractant protein-1 (MCP-1) without changing MCP-1 receptor (CCR2) surface expression. Pretreatment of THP-1 monocytes with RES or UA (0.3-10μM) for 15h resulted in the dose-dependent inhibition of H(2)O(2)-accelerated chemotaxis in response to MCP-1, but with an IC(50) of 0.4μM, UA was 2.7-fold more potent than RES.. Dietary UA is a potent inhibitor of monocyte dysfunction and accelerated atherosclerosis induced by diabetes. These studies identify ursolic acid as a potential therapeutic agent for the treatment of diabetic complications, including accelerated atherosclerosis, and provide a novel mechanism for the anti-atherogenic properties of ursolic acid.

Topics: Animals; Aortic Diseases; Atherosclerosis; Cardiovascular Agents; Cell Line; Chemokine CCL2; Chemotaxis, Leukocyte; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Dose-Response Relationship, Drug; Female; Humans; Hyperlipidemias; Kidney; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes; Oxidative Stress; Receptors, CCR2; Receptors, LDL; Resveratrol; Stilbenes; Time Factors; Triterpenes; Ursolic Acid

Topics: Abortion, Induced; Aortic Diseases; Cardiovascular Agents; Contraindications; Counseling; Female; Heart Diseases; Humans; Hypertension; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Infectious; Prenatal Care; Prenatal Diagnosis; Venous Thromboembolism

Topics: Animals; Aortic Diseases; Apoptosis; Atherosclerosis; Cardiovascular Agents; Caspases; Diabetes Mellitus, Experimental; Diabetic Angiopathies; DNA Damage; Female; Human Umbilical Vein Endothelial Cells; Humans; Male; Mitochondria; Monocytes; Plaque, Atherosclerotic; Triterpenes; Tumor Suppressor Protein p53; Ursolic Acid

Topics: Aortic Diseases; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Combined Modality Therapy; Humans; Treatment Outcome; Vascular Surgical Procedures

Urotensin II (UII) and its receptor UT are upregulated in the pathological setting of various cardiovascular diseases including atherosclerosis. However, their exact role in atherosclerosis remains to be determined. In the present study we used four strains of mice; wild-type (WT), UT(+) (a transgenic strain expressing human UT driven by the alpha-smooth muscle-specific, SM22, promoter), ApoE knockout (ko), and UT(+)/ApoE ko. All animals were fed high fat diet for 12 weeks. Western blot analysis revealed a significant increase in aortic UT expression in UT(+) relative to WT mice (P<0.05). Aortas of ApoE ko mice expressed comparable UT protein level to that of UT(+). Immunohistochemistry revealed the presence of strong expression of UT and UII proteins in the atheroma of UT(+), ApoE ko and UT(+)/ApoE ko mice, particularly in foam cells. Serum cholesterol and triglyceride levels were significantly increased in ApoE ko and in UT(+)/ApoE ko but not in UT(+) mice when compared to WT mice (P<0.0001). Analysis of aortas showed a significant increase in atherosclerotic lesion in the UT(+), ApoE ko and UT(+)/ApoE ko compared to WT mice (P<0.05). Oral administration of the UT receptor antagonist SB-657510A (30 microg/Kg/day gavage) for 10 weeks in a group of ApoE ko mice fed on high fat diet resulted in a significant reduction of lesion (P<0.001). SB-657510A also significantly reduced ACAT-1 protein expression in the atherosclerotic lesion of ApoE ko mice (P<0.05). The present findings demonstrate an important role for UT in the pathogenesis of atherosclerosis. The use of UT receptor antagonists may provide a beneficial tool in the management of this debilitating disease process.

Topics: Acetyl-CoA C-Acetyltransferase; Animals; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Blotting, Western; Cardiovascular Agents; Cholesterol, Dietary; Disease Models, Animal; Foam Cells; Humans; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microfilament Proteins; Muscle Proteins; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Promoter Regions, Genetic; Receptors, G-Protein-Coupled; Sulfonamides; Triglycerides; Urotensins

1. The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload-induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short-term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload-induced hypertrophy. 2. Twenty-six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS-GH group) or saline (AAS-P group) for 14 days. Sham-operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis. 3. Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS-P group than in the control group. However, in the AAS-GH group, PWSV was between that in the control and AAS-P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS-P and AAS-GH groups compared with control (10.34 +/- 1.29, 4.44 +/- 1.37 and 1.88 +/- 0.88%, respectively; P < 0.05) and was higher still in the AAS-P group compared with the AAS-GH group. 4. The present study has shown that short-term administration of GH to rats with chronic pressure overload-induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

Topics: Animals; Aorta; Aortic Diseases; Cardiovascular Agents; Chronic Disease; Constriction, Pathologic; Disease Models, Animal; Echocardiography; Fibrosis; Human Growth Hormone; Hypertrophy, Left Ventricular; Injections, Subcutaneous; Male; Myocardial Contraction; Myocardium; Rats; Rats, Wistar; Recombinant Proteins; Time Factors; Ventricular Function, Left; Ventricular Remodeling

In coronary artery bypass surgery, arterial grafts result in improved patency rates. However, these grafts frequently fail due to spasm. Papaverine has been used to prevent graft spasm, but its effect is short-lived. Botulinum toxin inhibits muscle contraction for about three months. We investigated the usefulness of botulinum toxin in preventing arterial grafts spasm in vitro. Samples of abdominal aorta from male Wistar rats were cut into 2 mm rings and treated with various doses of botulinum toxin or papaverine for 30 min. All rings were stimulated with KCl and noradrenaline. Tension was recorded using myography. We compared constriction caused by noradrenaline or KCl in rings treated with botulinum toxin, or papaverine, or physiological salt solution (PSS) (control). In the presence of KCl and noradrenaline, almost all concentrations of botulinum toxin completely inhibited arterial contraction when compared with controls. Spasm prevention was lost after 60 min in rings with papaverine but persisted for 120 min in rings with botulinum toxin. In the histological examination, arterial wall structure was not destroyed by botulinum toxin. Botulinum toxin prevented arterial graft spasm in vitro and had a longer lasting effect than papaverine, with no toxic effect on the artery.

Topics: Animals; Aorta, Abdominal; Aortic Diseases; Botulinum Toxins; Cardiovascular Agents; Dose-Response Relationship, Drug; In Vitro Techniques; Male; Myography; Norepinephrine; Papaverine; Potassium Chloride; Rats; Rats, Wistar; Spasm; Time Factors; Vasoconstriction; Vasoconstrictor Agents

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Aortic Diseases; Aortic Rupture; Atherosclerosis; Biomarkers; Cardiovascular Agents; Complementary Therapies; Disease Progression; Drugs, Chinese Herbal; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation Mediators; Lipids; Simvastatin

A total of 502 patients presenting in Utsunomiya city and its suburbs during a 10-year period were studied to determine the clinical features of ischemic heart disease and to identify coronary risk factors. The male/female ratio was 1.21, but the ratio decreased with increasing age. The duration of chest pain showed a continuous spectrum between angina and infarction, with a short duration of chest pain not being useful for excluding the diagnosis of myocardial infarction. Hypertension was more common than hypercholesterolemia in this study, although the prevalence of the latter increased slightly with time, along with the shift towards a modernized occupational pattern. Smoking was a more important risk factor for ischemic heart disease in younger individuals than in the elderly, and diabetes mellitus was highly associated with the development of myocardial infarction. The incidence of radiologically diagnosed cardiac hypertrophy and aortic calcification decreased over time. These changes may have resulted in part from improved blood pressure control and the development of new anti-hypertensive and cholesterol-lowering agents.

Topics: Age Factors; Alcohol Drinking; Aortic Diseases; Arteriosclerosis; Calcinosis; Cardiomegaly; Cardiovascular Agents; Chest Pain; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Hypertension; Japan; Male; Morbidity; Myocardial Ischemia; Occupations; Risk Factors; Smoking; Urban Population

Topics: Aminobenzoates; Aorta; Aortic Diseases; Cardiovascular Agents; Disease; Ergoloid Mesylates; Ergot Alkaloids; Leucine; para-Aminobenzoates; Thrombosis