losartan-potassium and Coronary-Artery-Disease

Im Rahmen der vorliegenden Studie sollte der Einfluss des Weichteilschadens auf das klinische Ergebnis nach offener Ellenbogenluxation untersucht werden.. Von Oktober 2008 bis August 2015 wurden insgesamt 230 Patienten mit Ellenbogenluxation behandelt. Diese retrospektive Studie umfasst 21 Fälle von offenen Ellenbogenluxationen. Das Durchschnittsalter der Patienten betrug 49 Jahre alt (20–83 Jahre), 6 Patienten waren weiblich (29%), 15 männlich (71%). Das Bewegungsausmaß des verletzten und unverletzten Ellenbogens wurde erhoben und das funktionelle Ergebnis u. a. mittels Mayo Elbow Performance Score (MEPS), Mayo Wrist Score (MWS) und dem Disability of Arm, Shoulder and Hand (DASH) Score erfasst. Zusätzlich wurden Komplikationen und Revisionsoperationen aufgezeichnet. Der Einfluss des Weichteilschadens (I°/II° offen vs. III° offen) und des Luxationstyps (einfach vs. komplex) auf das klinische Ergebnis wurde analysiert.. Offene Ellenbogenluxationen können mit einem zufriedenstellenden klinischen Ergebnis einhergehen. Insbesondere komplexe offene Ellenbogenluxationen sind jedoch sehr komplikationsbehaftet, wobei neurovaskuläre Komplikationen am häufigsten auftreten.. The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance.. The results indicated differential patterns of Inhibition of Return between the High and Low shape/weight based self-worth groups. The High group displayed increased inhibition of return for the shape/weight stimuli relative to control stimuli, while the Low group displayed reduced inhibition of return for the shape/weight stimuli compared to control stimuli. The ED group displayed a similar pattern of results to the High group, but this did not reach significance.. The current findings indicate that young women without an eating disorder who base their self-worth on shape/weight display a pattern of avoidance of shape/weight stimuli that is in direct contrast to those at low risk of developing eating disorders. The possible implications of these specific patterns of inhibition of return across those at varying levels of risk for an eating disorder are discussed along with their implications for intervention approaches.. These results indicated that Sr. An unusually high HbA

Topics: Activities of Daily Living; Acute Disease; Adalimumab; Adaptation, Physiological; Adenosine Triphosphate; Adipose Tissue; Administration, Intravaginal; Adolescent; Adsorption; Adult; Adverse Childhood Experiences; Age Distribution; Age Factors; Aged; Aged, 80 and over; Air Pollution, Indoor; Aldehyde Oxidase; Alginates; Alloys; alpha-Globins; Aluminum Hydroxide; Alveolar Bone Loss; Anaerobiosis; Anesthesia, General; Anesthetics; Animals; Anovulation; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Apoptosis; Bacillus cereus; Bacterial Typing Techniques; Bacteroidetes; Base Composition; Biocompatible Materials; Biofilms; Biological Availability; Biological Transport; Biosensing Techniques; Bipolar Disorder; Blood Glucose; Body Mass Index; Bone Regeneration; Boranes; Brachial Artery; Butyric Acid; Candida albicans; Carbon; Carcinoembryonic Antigen; Cell Differentiation; Cell Line, Tumor; Cell Respiration; Cell Survival; Cells, Cultured; Cerebrovascular Circulation; Charcoal; Child; Child Health; China; Chloride Channels; Chlorides; CHO Cells; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromium; Chronic Disease; Chronic Periodontitis; Circular Dichroism; Cities; Cohort Studies; Comamonadaceae; Comorbidity; Coronary Artery Disease; Corrosion; Cricetinae; Cricetulus; Cross Infection; Cross-Sectional Studies; Crowding; Culture Media; Cytokines; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes, Gestational; Diarylheptanoids; Diclofenac; Disability Evaluation; Diterpene Alkaloids; DNA; DNA Mutational Analysis; DNA, Bacterial; Drug Liberation; Drug Resistance, Multiple, Bacterial; Electrochemical Techniques; Electrodes; Electrolytes; Endothelium, Vascular; Enterococcus faecalis; Epithelial Cell Adhesion Molecule; Epithelial Cells; Erbium; Erythropoietin; Ethanol; Ethylenediamines; Fast Foods; Fatty Acids; Female; Fermentation; Ferric Compounds; Fibroblasts; Flavobacteriaceae; Fluorides; Fluorodeoxyglucose F18; Food Microbiology; Formaldehyde; Furaldehyde; Gamma Cameras; Gene Expression; Geologic Sediments; Glucose Tolerance Test; Glycated Hemoglobin; Glycolipids; Glycosylation; Gracilaria; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Guanine; Health Surveys; HeLa Cells; Hemoglobins, Abnormal; Hexosamines; High Fructose Corn Syrup; High-Intensity Interval Training; Hip Fractures; Hippocampus; HLA-B27 Antigen; Hospitalization; Housing; Humans; Hydrogen-Ion Concentration; Hydrolysis; Hydroxides; Hypercapnia; Hypertension; Hypocreales; Hypromellose Derivatives; Image Processing, Computer-Assisted; Incidence; Indole Alkaloids; Indonesia; Inflammation Mediators; Infrared Rays; Insulin Resistance; Intercalating Agents; Ion Transport; Ionophores; Japan; Kinetics; Kluyveromyces; Letrozole; Linear Models; Lipopolysaccharides; Liposomes; Liver; Lung Diseases; Magnesium Hydroxide; Magnetic Resonance Spectroscopy; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microbial Viability; Microscopy, Electron, Transmission; Middle Aged; Mitochondria; Mitochondria, Muscle; Molecular Docking Simulation; Molecular Structure; Muscle, Skeletal; Mutant Proteins; Mutation; Mutation, Missense; Nanocomposites; Nanoparticles; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating; Nucleic Acid Hybridization; Obesity; Occupational Exposure; Oceans and Seas; Odds Ratio; Organometallic Compounds; Osteogenesis; Ovulation Induction; Oxidation-Reduction; Particle Size; Periodontal Ligament; Permeability; Phaseolus; Phenotype; Philippines; Phosphatidylethanolamines; Phospholipids; Photochemical Processes; Phylogeny; Pichia; Pigmentation; Plant Extracts; Polycystic Ovary Syndrome; Polysaccharides; Postprandial Period; Pregnancy; Pregnancy Rate; Prevalence; Product Surveillance, Postmarketing; Progesterone; Progestins; Protein Engineering; Pseudomonas aeruginosa; Psoriasis; Public Facilities; Rats; Rats, Wistar; Receptors, Thyrotropin; Recombinant Proteins; Reproducibility of Results; Republic of Korea; Retrospective Studies; Rhodobacteraceae; Risk; Risk Assessment; Risk Factors; RNA, Ribosomal, 16S; ROC Curve; Saccharomyces cerevisiae; Salinity; Saliva; Seawater; Seaweed; Sensitivity and Specificity; Sequence Analysis, DNA; Sex Factors; Silver Compounds; Smokers; Social Class; Socioeconomic Factors; Soil Microbiology; Solubility; Soy Foods; Spectrometry, Mass, Electrospray Ionization; Spondylitis, Ankylosing; Staphylococcus aureus; Static Electricity; Steroids; Strontium; Sucrose; Surface Properties; Survival Rate; Sweden; Swine; Synapses; Synchrotrons; Tandem Mass Spectrometry; Tannins; Tea; Temperature; Terpenes; Thalidomide; Thermodynamics; Thiadiazoles; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy; Time Factors; Tissue Distribution; Titanium; Toilet Facilities; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Ubiquinone; Urinary Tract Infections; Vaginal Creams, Foams, and Jellies; Venezuela; Vitamin K 2; Waist Circumference; Waste Disposal, Fluid; Wastewater; Water Microbiology; Water Pollutants, Chemical; Whole Body Imaging; X-Ray Diffraction; Young Adult; Ytterbium; Yttrium; Yttrium Radioisotopes; Zinc Compounds

Red blood cell distribution width (RDW) can predict mortality in cardiovascular disease. However, the underlying mechanisms of the beneficial prognostic marker remain unknown. The purpose of this study was to investigate whether the RDW is related to impaired exercise tolerance and exercise training (ET) effect on RDW in patients with coronary artery disease (CAD).Seventy-eight patients who underwent ET by supervised bicycle ergometer during 3 weeks served as the ET group whereas 30 patients who did not undergo ET were the control group. Exercise stress test with cardiopulmonary analysis was performed in the ET group. Peak oxygen uptake (from 14.1 ± 4.0 to 15.1 ± 3.8 mL/kg/minute, P < 0.05) significantly increased in the ET group. Although RDW and serum erythropoietin concentration (EP) before the observation period did not differ between the ET and control groups, RDW (from 44.4 ± 4.7 to 43.4 ± 3.8 fL, P < 0.01) and EP (from 27.9 ± 15.8 to 22.9 ± 8.2 mIU/mL, P < 0.005) significantly decreased in the ET group, however, these parameters did not change in the control group. In the ET group, RDW was negatively correlated with peak oxygen uptake (r = -0.55, P < 0.01) and the changes in RDW before and after ET were positively correlated with the changes in EP (r = 0.39, P < 0.005).Thus, ET increases exercise tolerance and decreases RDW in association with increased oxygen uptake in patients with CAD.

Topics: Aged; Aged, 80 and over; Coronary Artery Disease; Erythrocyte Indices; Erythropoietin; Exercise; Exercise Test; Exercise Tolerance; Female; Humans; Male; Middle Aged; Oxygen Consumption

Exercise training partially corrects endothelial dysfunction in patients with coronary artery disease (CAD). Growth factors like vascular endothelial growth factor (VEGF) as well as erythropoietin (EPO) are known to modulate the bioavailability of nitric oxide and, thereby, contribute to the maintenance of a normal vascular tone. The aim of the present study was to determine the impact of 4 weeks of exercise training on circulating growth factors and to elucidate their involvement in the training-induced changes in vasomotion in patients with CAD.. A total of 39 patients were enrolled (training group: n = 20; control group: n = 19). At start of study and after 4 weeks, average peak flow velocity (APV) of the left internal mammary artery (LIMA) in response to acetylcholine was measured invasively in the treatment and control groups. Serum concentrations of VEGF and EPO were determined by enzyme-linked immunosorbent assay. After exercise training, LIMA APV in response to acetylcholine was increased by 93% (from 69 ± 17% at start of study to 133 ± 16% at 4 weeks, p < 0.01 vs. start of study and control). At start of study, there was no association between any of the vascular growth factors and endothelial function. However, after exercise training a close correlation was apparent between the acetylcholine-induced change in APV and EPO (r = 0.69, p < 0.01) and VEGF (r = 0.76, p < 0.01) serum concentrations. In the control group, these correlations were not evident and there was no change in endothelial function either.. Exercise training improves agonist-mediated endothelium-dependent vasodilatation in CAD, partially through a restoration of the endothelial response to EPO and VEGF.

Topics: Aged; Analysis of Variance; Blood Flow Velocity; Chi-Square Distribution; Coronary Artery Disease; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Exercise Therapy; Female; Germany; Humans; Linear Models; Male; Mammary Arteries; Middle Aged; Regional Blood Flow; Time Factors; Treatment Outcome; Vascular Endothelial Growth Factor A; Vasodilation; Vasodilator Agents

Vasoprotective effects of erythropoietin in animal models are mediated by endothelium-derived NO and/or mobilization of EPCs (endothelial progenitor cells) and may be enhanced by ischaemia: whether they are present in humans is unknown. We examined whether the erythropoietin analogue darbepoetin improves FMD (flow-mediated dilatation), a measure of endothelium-derived NO, and whether this is influenced by preceding I/R (ischaemia/reperfusion). A total of 36 patients (50-75 years) with stable coronary artery disease were randomized to receive a single dose of darbepoetin (300 μg) or saline placebo. FMD was measured at the brachial artery using high-resolution ultrasound. CD133⁺/CD34⁺/VEGFR2⁺ (vascular endothelial growth factor receptor 2) circulating EPCs were enumerated by flow cytometry. Measurements were made immediately before darbepoetin/placebo and at 24 h, 72 h and 7 days. At 24 h, FMD was repeated after 20 min of I/R of the upper limb. A further group of 11 patients was studied according to the same protocol, all receiving darbepoetin, with omission of forearm I/R at 24 h. Immunoreactive erythropoietin peaked at 24 h and remained elevated at approximately 50-fold of baseline at 72 h. FMD did not differ significantly between groups at 24 h (before I/R). At 72 h (48 h after I/R), FMD was greater (by 2.3±0.5% in the darbepoetin compared with the placebo group, a 66% increase over baseline; P<0.001) and greater than FMD at the same time point without preceding I/R (P<0.01). Increases in CD133⁺/CD34⁺/VEGFR2⁺ cells after darbepoetin did not differ according to the presence or absence of preceding I/R. Preceding I/R is required for darbepoetin to enhance endothelial function, possibly by increasing expression of the erythropoietin receptor and by a mechanism likely to involve Akt/NO rather than circulating EPCs.

Topics: Aged; Biomarkers; Blood Pressure; Coronary Artery Disease; Cytokines; Darbepoetin alfa; Endothelial Cells; Endothelium; Erythropoietin; Female; Humans; Inflammation; Male; Middle Aged; Myocardial Reperfusion Injury; Platelet Activation; Stem Cells; Vasomotor System

[Figure: see text].

Topics: Animals; Blood Pressure; Coronary Artery Disease; Cross-Sectional Studies; Erythropoietin; Female; Humans; Hypertension; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Middle Aged; Prospective Studies; Receptor, Platelet-Derived Growth Factor alpha; Serine Endopeptidases; Vasoconstriction

Topics: Benzhydryl Compounds; Coronary Artery Disease; Diabetes Mellitus, Type 2; Erythrocyte Count; Erythrocytes; Erythropoietin; Ferritins; Glucosides; Hematocrit; Humans; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors

Erythroferrone (ERFE) is an erythroid hormone putatively involved in stress erythropoiesis. Its regional clearance and circulating form in humans, as well as levels in normal health and coronary disease remain unclear.. To establish a reference interval, ERFE was measured in 155 healthy volunteers using the Intrinsic LifeSciences ELISA. To identify trans-organ gradients in ERFE, regional blood sampling was undertaken in patients (n = 13) undergoing clinically indicated cardiac catheterisation. The Intrinsic ELISA was assessed for reproducibility, stability, linearity and possible cross-reactivity, interference and anticoagulant effects. Circulating forms of ERFE were evaluated by HPLC.. In healthy individuals, the median concentration of ERFE was 0.51 ng/mL (IQR: 0.12-1.25), with men (n = 78) having higher levels than women (n = 77) (0.67 vs 0.32 ng/mL, p = 0.0001). ERFE concentrations in trans-organ sampling revealed no clear organ of clearance or production. Samples with high endogenous ERFE levels were suppressed by haemoglobin (≥2 g/L), bilirubin (≥200 µmol/L), lipaemia (>1 g/L), and freeze thawing (≥2 cycles), but this was not observed with low ERFE concentrations. Endogenous ERFE immunoreactivity was 46% higher in EDTA plasma compared with serum and lithium heparin plasma. On SE-HPLC, ERFE eluted as intact and cleaved forms.. We provide a useful reference range for ERFE in EDTA plasma. We found no specific site of secretion or clearance. The Intrinsic ELISA performed adequately but is limited by interference and stability when endogenous levels are high. Circulating forms are multiple and complex.

Topics: Adult; Aged; Biomarkers; Cardiac Catheterization; Chromatography, High Pressure Liquid; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Erythropoiesis; Erythropoietin; Female; Ferritins; Healthy Volunteers; Hepcidins; Humans; Iron; Male; Middle Aged; Peptide Hormones; Reference Values; Young Adult

To investigate the relationship between electrocardiographic changes and erythropoietin (EPO) level in stable coronary artery disease (CAD) patients with autonomic nerve functional damage.. Clinical data of 96 stable CAD patients who were treated in our hospital from January 2017 to December 2019 were retrospectively analyzed. All patients were grouped according to whether autonomic nerve function damage was combined; the baseline characteristic data and the morphological characteristics of ECG scattergram were compared between 2 groups, and the relationship between ECG scattergram and EPO level & autonomic nerve function was analyzed.. The levels of EPO and red cell volume distributing width (RDW) in stable CAD patients with autonomic nerve dysfunction were significantly higher than that of CAD patients without autonomic nerve dysfunction (p<0.05). The length of scattergram in stable CAD patients with autonomic nerve dysfunction was significantly shorter than that of those without autonomic nerve dysfunction (p<0.05). The cometary sign proportion of ECG scattergram in stable CAD patients with autonomic nerve dysfunction was significantly lower than that of stable CAD patients without autonomic nerve dysfunction (p<0.05). There was negative correlation between EPO levels and scattergram length in stable CAD patients with and without autonomic nerve dysfunction (r=0.44, p=0.02). There was no correlation between EPO levels and scatter width in stable CAD patients with and without autonomic nerve dysfunction (r=0.10, p=0.58). The results of binary logistic regression analysis showed that EPO level was the independent risk factor for the occurrence of autonomic dysfunction in patients with stable CAD (p<0.05). The length of scattergram was the independent protective factor of autonomic nerve function impairment in patients with stable CAD (p<0.05). The AUC of EPO level and scattergram was 0.74 and 0.72 respectively, both of which have similar prediction value.. The level of EPO in stable CAD patients with autonomic nerve dysfunction was related to the change of ECG; and the EPO level and scattergram length can be used to predict the occurrence risk of autonomic nerve dysfunction.

Topics: Autonomic Pathways; Coronary Angiography; Coronary Artery Disease; Electrocardiography; Erythropoietin; Female; Humans; Male; Middle Aged; Retrospective Studies

Red cell distribution width (RDW) is a cardiac marker for risk stratification and prognostic evaluation of coronary artery disease (CAD); however, the underlying mechanism remains unclear. Erythropoietin (EPO), a crucial factor affecting erythropoiesis, has been reported to be a protective molecule regulating the process of myocardial ischemia and relevant damage. No study has as yet reported the relationship between RDW and endogenous EPO in CAD patients. This cross-sectional study aimed to establish the association between endogenous EPO levels and increases in RDW in CAD patients.. Two hundred participants who underwent coronary arteriography were recruited from July 2015 to October 2015. The participants were divided into CAD and non-CAD groups on the basis of angiography diagnosis. Demographic data were obtained through personal interviews and general clinical methods.. RDW and EPO levels in the CAD group were higher than those in the non-CAD group. The correlation between RDW and EPO levels was statistically significant among CAD patients (r=0.411, P<0.001). The increases in EPO and RDW were related to the prevalence of CAD. The levels of RDW were correlated to endogenous EPO levels in CAD patients.. Increased EPO and RDW might be risk factors for CAD. Endogenous EPO levels are associated with increases in RDW in CAD patients.

Topics: Aged; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Erythrocyte Indices; Erythropoietin; Female; Humans; Linear Models; Logistic Models; Male; Middle Aged; Risk Factors

Erythropoietin (EPO) deficiency or inadequate EPO secretion in response to bleeding may result in profound or prolonged anaemia after cardiac surgery.. The aim of the study was to evaluate the changes in EPO secretion in patients undergoing off-pump coronary artery bypass grafting (OPCAB).. Blood samples from 43 patients (mean age 65.1 ± 7.6 years) were obtained before surgery and on the 1st, 2nd, and 6th day post isolated OPCAB. EPO levels ≥ 4.3 mIU/mL were considered normal.. Thirteen (30%) patients had the preoperative EPO level below normal range even though their preoperative haemoglobin was ≥ 13 g/dL. In patients with basal EPO deficiency lower peak EPO levels were observed compared to the group with normal basal EPO levels, even though reduction in haemoglobin concentrations was comparable in both groups. Moreover, lower reticulocytosis was noted on day 1 (8.5 ± 4.0‰ vs. 11.7 ± 4.4‰; p = 0.04) and a tendency toward lower values was seen on day 2 (9.6 ± 4.3‰ vs. 13.0 ± 5.8‰; p = 0.07) among patients with preoperative EPO deficiency.. Erythropoietin deficiency is common in patients scheduled for OPCAB, and it results in diminished increase in EPO secretion in response to bleeding. Consequently, in patients with EPO deficiency, reticulocytosis is lower than it could be predicted based on the observation of patients with normal EPO levels and similar blood loss.

Topics: Aged; Coronary Artery Bypass, Off-Pump; Coronary Artery Disease; Erythropoietin; Female; Humans; Male; Middle Aged; Postoperative Hemorrhage

From our previous clinical trials, intracoronary infusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells ((mob)PBMCs) proved to be effective in improving myocardial contractility and reducing infarct volume in acute myocardial infarction. We tested the effect of priming (mob)PBMCs with erythropoietin (EPO) to augment its therapeutic efficacy.. (mob)PBMCs were obtained from healthy volunteers after a 3-day subcutaneous injection of G-CSF (10 μg/kg). About 40% of (mob)PBMCs were EPO receptor (EPOR) (+) and responded to 6 h EPO-priming (10 IU/mL) by increasing the expression of vasculogenic factors (i.e. IL8, IL10, bFGF, PDGF, MMP9) and adhesion molecules (i.e. integrin αV, β1, β2, β8) through the JAK2 and Akt pathway. These responses were also observed in PBMCs from elderly patients with coronary disease. The conditioned media from EPO-primed (mob)PBMCs contained various cytokines such as IL8, IL10, TNFα, and PDGF, which enhanced the migration and tube formation capability of endothelial cells. EPO-primed (mob)PBMCs also showed increased adhesion on endothelial cells or fibronectin. Augmented vasculogenic potential of EPO-primed (mob)PBMCs was confirmed in a Matrigel plug assay, ischaemic hindlimb, and myocardial infarction models of athymic nude mice. There were two action mechanisms: (i) cellular effects confirmed by direct incorporation of human (mob)PBSCs into mouse vasculature and (ii) indirect humoral effects confirmed by the therapeutic effect of the supernatant of EPO-primed (mob)PBMCs.. Brief ex vivo EPO-priming is a novel method to augment the vasculogenic potential of human (mob)PBMCs, which would help to achieve better results after intracoronary infusion in myocardial infarction patients.

Topics: Angiogenic Proteins; Animals; Bone Marrow Cells; Case-Control Studies; Cell Adhesion; Cell Adhesion Molecules; Cells, Cultured; Coronary Artery Disease; Culture Media, Conditioned; Cytokines; Disease Models, Animal; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hindlimb; Humans; Injections, Subcutaneous; Ischemia; Janus Kinase 2; Leukocytes, Mononuclear; Male; Mice, Nude; Muscle, Skeletal; Myocardial Infarction; Neovascularization, Physiologic; Peripheral Blood Stem Cell Transplantation; Proto-Oncogene Proteins c-akt; Recombinant Proteins; Regeneration; Signal Transduction; Time Factors

Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (≈70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-α and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-α expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-α production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease.

Topics: Animals; Apoptosis; Cardiovascular Agents; Cell Line; Coronary Artery Disease; Disease Models, Animal; Erythropoietin; Female; Human Umbilical Vein Endothelial Cells; Humans; Male; Matrix Metalloproteinase 9; Peptide Fragments; Proto-Oncogene Proteins c-akt; Rabbits; Tumor Necrosis Factor-alpha

Although higher red cell distribution width (RDW) has recently been reported to be associated with increased mortality independent of anemia in patients with heart failure and those with coronary artery disease (CAD), the mechanism underlying this association is unknown. We hypothesized that higher RDW may reflect neurohumoral activation and a chronic inflammatory state that each contribute to adverse clinical outcomes in these populations. We measured RDW and plasma levels of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hs-CRP) in 226 consecutive patients undergoing cardiac catheterization for CAD (age, 67 +/- 8 years; males, 77%; RDW, 45.8 +/- 3.3 fL; hemoglobin, 13.2 +/- 1.4 g/dL; BNP, median [interquartile range], 26.0 [9.0-58.4] pg/mL; hs-CRP, 679 [345-1920] ng/mL). Plasma BNP (r = 0.21, P < 0.01) but not hs-CRP (r = 0.04, P > 0.1) levels correlated with RDW. After adjustment for potential confounders including age, gender, body mass index, glomerular filtration rate, hemoglobin, and known hemodynamic determinants of BNP, including elevated left ventricular end-diastolic pressure and volume and slow left ventricular relaxation, RDW was independently predicted by BNP (r(2) = 0.058, P < 0.001). In conclusion, elevated BNP levels are independently associated with higher RDW in patients with CAD. Neurohumoral activation may be a mechanistic link between increased RDW and adverse clinical outcomes in this population.

Topics: Aged; Blood Cell Count; C-Reactive Protein; Cardiac Catheterization; Cell Size; Coronary Artery Disease; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Reference Values; Statistics as Topic; Survival Rate

As regular physical exercise improves endothelial dysfunction and promotes cardiovascular health, we investigated the effect of training on angiogenesis by measuring the number of circulating endothelial progenitor cells (EPC), the level of EPC-mobilizing growth factors and tested vascular function by flow-mediated dilation (FMD) in patients with coronary artery disease (CAD) and cardiovascular risk factors (CVRF). In addition, degradation products of the NO pathway (NOx) were determined.. Twenty patients with documented CAD and/or CVRF joined a 12-week supervised running training. Circulating EPCs--defined by the surface markers CD34, KDR and CD133--were measured at baseline and after exercise training by flow cytometry. We found a significant increase in circulating EPCs (2.9+/-0.4-fold increase; P < .0001), which was positively correlated with both, the change of FMD (r = .81, P < .001) and the increase of NOx synthesis (r = .83, P < .001). Plasma VEGF and erythropoietin did not change in response to exercise. However, we observed a positive correlation between the number of EPCs and erythropoietin at baseline (r = .70, P < .01) and after training (r = .73, P < .01).. Regular exercise training augments the number of circulating EPCs in patients with CVRF and CAD and is associated with improved vascular function and NO synthesis.

Topics: Adult; Coronary Artery Disease; Endothelium, Vascular; Erythropoietin; Female; Flow Cytometry; Humans; Male; Middle Aged; Neovascularization, Physiologic; Nitrates; Nitric Oxide; Nitrites; Physical Endurance; Risk Factors; Stem Cells; Vascular Endothelial Growth Factor A; Vasodilation

Topics: Acute Disease; Coronary Artery Disease; Erythropoietin; Humans; Insulin-Like Growth Factor I; Kidney Diseases; Myocardial Infarction; Myocardial Ischemia; Syndrome

Topics: Anemia; C-Reactive Protein; Coronary Artery Disease; Cytomegalovirus Infections; Erythropoietin; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Treatment Outcome