cardiovascular-agents and Autoimmune-Diseases

Chronic wounds are a major cause of morbidity and mortality. Approximately 20% to 23% of nonhealing wounds that are refractory to vascular intervention have other causes, including vasculitis, pyoderma gangrenosum, and other autoimmune diseases. The purpose of this article was to review the literature across medical and surgical specialties with regard to refractory chronic wounds associated with vasculitis and autoimmune diseases and to delineate clinical outcomes of these wounds in response to vascular and other interventions.. An electronic search encompassing MEDLINE, PubMed, Cochrane Library, and Scopus was completed using the following search terms: rheumatoid arthritis; systemic sclerosis; systemic lupus erythematosus; antineutrophil cytoplasmic antibody-associated vasculitis; mixed connective tissue disease; antiphospholipid syndrome; pyoderma gangrenosum; thromboangiitis obliterans; cryoglobulinemia; hydroxyurea; sickle cell; atrophie blanche; livedoid vasculitis; cholesterol emboli; calciphylaxis; antiphospholipid antibodies; prothrombotic; combined with the terms: chronic wound and leg ulcer. Full-text articles published in English up to March 1, 2016, that investigated the clinical outcomes of chronic wounds associated with autoimmune diseases were included. Review articles and evaluations of management of chronic wounds were also reviewed. Primary outcomes included in the review were amputation, ulcer healing, reduction in wound size, overall survival, and freedom from reintervention. Owing to the heterogeneity of data reporting among articles, qualitative analysis is also reported.. Vasculitis and autoimmune diseases play a role in 20% to 23% of patients with chronic lower extremity ulcers. Furthermore, patients with autoimmune disease have a significantly high rate of split thickness skin graft failure (50% compared to 97% in patients without autoimmune disease; P = .0002). The management of leg ulcers associated with autoimmune diseases is discussed.. Autoimmune and vasculitic causes should be considered in patients with chronic wounds who do not respond to appropriate vascular intervention and standard local wound care. A multidisciplinary approach with the involvement of rheumatologists allows investigation for underlying systemic disease and improves clinical outcomes for many of these challenging patients.

Topics: Anemia, Sickle Cell; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antiphospholipid Syndrome; Antirheumatic Agents; Antisickling Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Calciphylaxis; Cardiovascular Agents; Chronic Disease; Cryoglobulinemia; Diagnosis, Differential; Embolism, Cholesterol; Erythema Nodosum; Humans; Hydroxyurea; Leg Ulcer; Panniculitis; Pyoderma Gangrenosum; Steroids; Thromboangiitis Obliterans; Vasculitis; Wound Healing

The role of chemokines and their receptors in controlling several physiological and pathological processes has only become evident in the last couple of years. From a sole function of chemo-attraction, our view on chemokine receptor activation has switched to the regulation of pleiotropic signaling pathways influencing numerous molecular and cellular processes. The large number of chemokines and receptors and hence possible combinations of chemokine-chemokine receptor interactions, as well as the expression profiles of chemokines and chemokine receptors within particular cell types, has contributed to the complexity of chemokine receptor signaling as we see it today. The chemokine CCL2 and its main chemokine receptor CCR2 have been implicated in the pathogenesis of several different disease processes, including vascular permeability and attraction of immune cells during metastasis, a number of different neurological disorders, autoimmune disease, obesity, and atherosclerosis. Here we review recent findings on the role of the CCL2-CCR2 axis in the regulation of these diseases. We believe that research has only gained a first glimpse of what chemokines can control and what the underlying mechanisms are. There is certainly more to be found that will - with high certainty - have strong implications for clinical applications in the near future.

Topics: Animals; Antineoplastic Agents; Autocrine Communication; Autoimmune Diseases; Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System; Chemokine CCL2; Drug Design; Humans; Immunosuppressive Agents; Metabolic Syndrome; Molecular Targeted Therapy; Neoplasms; Nervous System Diseases; Receptors, CCR2; Signal Transduction; Tumor Microenvironment

Morbidities related to atherosclerosis, such as acute coronary syndromes (ACS) including unstable angina and myocardial infarction, remain leading causes of mortality. Unstable plaques are inflamed and infiltrated with macrophages and T lymphocytes. Activated dendritic cells interact with T cells, yielding predominantly Th1 responses involving interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), while the role of interleukin 17 (IL-17) is questionable. The expansion of CD28nullCD4 or CD8 T cells as well as pattern recognition receptors activation (especially Toll-like receptors; TLR2 and TLR4) is characteristic for unstable plaque. Inflammation modifies platelet and fibrin clot characteristics, which are critical for ACS. Understanding of the inflammatory mechanisms of atherothrombosis, bridging inflammation, oxidative stress and immune regulation, will allow for the detection of subjects at risk, through the use of novel biomarkers and imaging techniques including intravascular ultrasound, molecular targeting, magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Moreover, understanding the specific inflammatory pathways of plaque rupture and atherothrombosis may allow for immunomodulation of ACS. Statins and anti-platelet drugs are anti-inflammatory, but importance of immune events in ACS warrants the introduction of novel, specific treatments directed either on cytokines, TLRs or inflammasomes. While the prime time for the introduction of immunologically inspired diagnostic tests and treatments for atherosclerosis have not come yet, we are closer than ever before to finally being able to benefit from this vast body of experimental and clinical evidence. This paper provides a comprehensive review of the role of the immune system and inflammation in ACS.

Topics: Acute Coronary Syndrome; Animals; Anti-Inflammatory Agents; Atherosclerosis; Autoimmune Diseases; Bacterial Infections; Cardiovascular Agents; Cytokines; Dendritic Cells; Diagnostic Imaging; Disease Models, Animal; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammasomes; Inflammation; Macrophages; Mast Cells; Matrix Metalloproteinases; Molecular Targeted Therapy; Myocardial Reperfusion Injury; Oxidative Stress; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Receptors, Pattern Recognition; Rupture, Spontaneous; T-Lymphocyte Subsets; Thrombophilia

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.

Topics: Animals; Anti-Asthmatic Agents; Antineoplastic Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Asthma; Autoimmune Diseases; Bone Density Conservation Agents; Cardiovascular Agents; Cerebrovascular Disorders; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Neoplasms; Nervous System Diseases; Neuroprotective Agents; Organ Transplantation; Osteoporosis; Sepsis

Topics: Anti-Inflammatory Agents; Autoimmune Diseases; Autoimmunity; Cardiovascular Agents; Cardiovascular Diseases; Drug Design; Humans; Immunomodulation; Molecular Targeted Therapy; Rheumatic Diseases; Rheumatoid Vasculitis; Systemic Vasculitis

Myocarditis is considered one of the major causes of dilated cardiomyopathy. Hepatocyte growth factor (HGF) has pleiotropic activities that promote tissue regeneration and facilitate functional improvement of injured tissue. We investigated whether the epicardial sustained-release of HGF, using gelatin hydrogel sheets, improves cardiac function in a chronic myocarditis rat model.. Six weeks after Lewis rats were immunized with porcine cardiac myosin to establish autoimmune myocarditis, HGF- or normal saline (NS)-incorporated gelatin hydrogel sheets were applied to the epicardium (G-HGF and G-NS, respectively). At either 2 or 4 weeks after treatment, these were compared with the Control myocarditis group. Cardiac function was evaluated by echocardiography and cardiac catheterization. Development of fibrosis was determined by histological study and expression of transforming growth factor-β1 (TGF-β1). Bax and Bcl-2 levels were measured to evaluate apoptotic activity.. At both points, fractional shortening and end-systolic elastance were higher in the G-HGF group than in the Control and G-NS groups (P < 0.01). Fractional shortening at 2 weeks of each group were as follows: 31.0 ± 0.9%, 24.8 ± 2.7% and 48.6 ± 2.6% (Control, G-NS and G-HGF, respectively). The ratio of the fibrotic area of the myocardium was lower in the G-HGF group than in the Control and G-NS groups at 2 weeks (G-HGF, 8.8 ± 0.9%; Control, 17.5 ± 0.2%; G-NS, 15.6 ± 0.7%; P < 0.01). The ratio at 4 weeks was lower in the G-HGF group than in the G-NS group (10.9 ± 1.4% vs 18.5 ± 1.3%; P < 0.01). The mRNA expression of TGF-β1 in the G-HGF group was lower than in the Control group at 2 weeks (0.6 ± 0.1 vs 1.1 ± 0.2) and lower than that in the G-NS group at 4 weeks (0.7 ± 0.1 vs 1.3 ± 0.2). The Bax-to-Bcl-2 ratios at both points were lower in the G-HGF group than in the Control group.. Sustained-released HGF markedly improves cardiac function in chronic myocarditis rats. The antifibrotic and antiapoptotic actions of HGF may contribute to the improvement. HGF-incorporated gelatin hydrogel sheet can be a new therapeutic modality for myocarditis.

Topics: Animals; Apoptosis; Autoimmune Diseases; bcl-2-Associated X Protein; Cardiac Myosins; Cardiovascular Agents; Chemistry, Pharmaceutical; Chronic Disease; Delayed-Action Preparations; Disease Models, Animal; Drug Carriers; Fibrosis; Gelatin; Gene Expression Regulation; Hepatocyte Growth Factor; Hydrogels; Immunization; Male; Myocardial Contraction; Myocarditis; Myocardium; Rats; RNA, Messenger; Swine; Time Factors; Transforming Growth Factor beta1; Ventricular Function, Left

Diastolic heart failure (DHF) remains unexplained in some patients with recurrent admissions after full investigation. A study was directed for screening SLE and systemic autoimmune connective tissue disorders in recurrent unexplained DHF patients admitted at a short-stay and intermediate care unit. It was found that systemic autoimmune conditions explained 11% from all of cases. Therapy also prevented new readmissions. Autoimmunity should be investigated in DHF.

Topics: Abortion, Habitual; Aged; Aged, 80 and over; Autoimmune Diseases; Cardiovascular Agents; Connective Tissue Diseases; Critical Care; Delayed Diagnosis; Female; Heart Failure, Diastolic; Humans; Lupus Erythematosus, Systemic; Male; Mass Screening; Middle Aged; Mitral Valve Insufficiency; Pregnancy; Prospective Studies; Recurrence; Spain

Patients with chronic kidney disease (CKD) frequently suffer from heart disease as well. The combination of the two processes can exacerbate inflammation, resulting in increases in both resistance to erythropoietin (EPO) and mortality.. The aim of this study was to determine the prevalence of heart disease in a representative group of non-dialysis patients with stage 4-5 CKD, and the influence of that entity on EPO requirements and on mortality during a period of 36 months.. 134 patients (68% on EPO at the beginning, increasing to 72.3% during follow-up) were monitored for 36 months. To evaluate the dose-response effect of EPO therapy, we used the erythropoietin resistance index (ERI) calculated as the weekly weight-adjusted dose of EPO divided by the haemoglobin level. The ERI was determined both initially and during the last six months before the end of the study.. 39 patients (29.1%) had history of heart disease; 22 (16.4%) had suffered from heart failure (HF). The ERI was higher in patients with a history of heart disease or HF and those treated with drugs acting on the renin-angiotensin system (ACE inhibitors or ARBs). Using ERI as the dependent variable in the multivariate analysis, the variables that composed the final model were ferritin, haemoglobin, glomerular filtration rate and history of HF. The 36 month mortality rate (n=39 patients) was higher in the group having ERI above the median (2.6IU/week/kg/gram of haemoglobin in 100ml) (P=.002), and in the groups with heart disease (P=.001) or HF (P=.001) according to the Kaplan-Meier survival analysis.. Patients with history of heart disease or HF have a higher ERI, and all of these characteristics are associated with lower survival. ERI can be considered a marker for risk of death in the short to-medium term.

Topics: Aged; Aged, 80 and over; Anemia; Autoimmune Diseases; Cardio-Renal Syndrome; Cardiovascular Agents; Comorbidity; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Resistance; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Heart Diseases; Heart Failure; Hemoglobins; Humans; Kaplan-Meier Estimate; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Severity of Illness Index

Regardless of the origin, injury to the heart can result in cardiomyocyte hypertrophy, fibrosis, and cell death. Myocarditis often progresses to dilated cardiomyopathy (DCM), a major cause of heart failure. In our study, we used a rat model of myosin-induced experimental autoimmune myocarditis (EAM), in which the heart transits from an acute phase (inflammatory myocarditis) to a chronic phase (remodeling and DCM). Our objective was to investigate whether T-3999, a novel phenylpyridazinone, can reduce this progression. Four weeks after myosin injection, T-3999 was administered daily to male Lewis rats in two doses (3 and 10 mg/kg, orally). Four weeks later, treatment was terminated; hemodynamic and echocardiographic measurements were performed; hearts were excised for histopathology and estimation of histamine, mRNA, and protein levels. Mortality rate was reduced by drug treatment. T-3999 reduced % fibrosis and tissue collagen III. Profibrotic markers-transforming growth factor-β(1), tumor necrosis factor-α, and galectin-3--were attenuated by treatment. Mast cell density and degranulation, and tissue histamine concentration were also reduced. This indicates an anti-inflammatory effect of the drug in reducing fibrosis. Hypertrophy was reduced as reflected by reduced myocyte diameter and natriuretic peptide expression. T-3999 treatment increased the sarcoendoplasmic reticulum Ca(2+) ATPase 2 protein level and improved several cardiac function parameters. The reduction of the remodeling process and improvement in myocardial function suggest an effect of T-3999 in attenuating ventricular remodeling in post-myocarditis DCM.

Topics: Animals; Autoimmune Diseases; Cardiomyopathy, Dilated; Cardiovascular Agents; Cell Degranulation; Cytokines; Disease Models, Animal; Disease Progression; Fibrosis; Hemodynamics; Histamine Release; Male; Mast Cells; Myocarditis; Myosins; Pyridazines; Rats; Rats, Inbred Lew; Time Factors; Ultrasonography; Ventricular Remodeling

Topics: Acute Disease; Adjuvants, Immunologic; Autoantibodies; Autoantigens; Autoimmune Diseases; B-Lymphocytes; Cardiovascular Agents; Chronic Disease; DNA; Humans; Immunoglobulin G; Immunoglobulin M; Immunosuppressive Agents; Methylhydrazines; Myocarditis; Myocardium; Recurrence; T-Lymphocytes; Virus Diseases

Topics: Adult; Aged; Analgesics; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Antibodies, Antinuclear; Anticoagulants; Autoimmune Diseases; Cardiovascular Agents; Chemical and Drug Induced Liver Injury; Dopamine Antagonists; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Time Factors

The development of an autoantibody to human Factor VIII is rare and presents many problems for diagnosis and treatment. We have seen several cases at our institution recently with widely heterogenous clinical and laboratory presentations. A wide range of treatment modalities were used in these cases with no gold standard of treatment or widely accepted guidelines existing. This has prompted us to examine all cases of this condition presenting at Fremantle Hospital over the last decade. We describe four cases which demonstrate the heterogeneity of this condition and its treatment and review the recent literature on the subject.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoantibodies; Autoimmune Diseases; Azathioprine; Breast Neoplasms; Cardiovascular Agents; Cardiovascular Diseases; Chlorambucil; Cyclophosphamide; Factor VIII; Female; Hematoma; Hemophilia A; Humans; Immunoglobulin G; Immunosuppressive Agents; Infections; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Neoplasms, Multiple Primary; Partial Thromboplastin Time; Prednisolone; Retrospective Studies

Topics: Autoimmune Diseases; Cardiovascular Agents; Humans; Hypersensitivity; Myocarditis