Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Committee reviewed cardiac involvement in the antiphospholipid antibody syndrome. The Committee's recommendations are: Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review). Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulation for those who have suffered thrombosis in the absence of atherosclerosis, but recognizes that developing data may support the use of antiplatelet agents instead. Intracardiac thrombi: the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction: the Committee has no recommendations on this aspect of cardiac disease. Pulmonary hypertension: the Committee recommends intensive anticoagulation with warfarin and clinical trials of bosentan, epoprostenol and other new agents.
Lupus 2003
PMID:Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report. 1289 91

Beta2-Glycoprotein I (beta2-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome (APS). We recently reported that oxidized LDL(oxLDL) is subsequently targeted by beta2-GPI and anti-beta2-GPI auto-Abs and that-carboxyl variants of 7-ketocholesteryl esters, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and 7-ketocholesteryl-12-carboxy (keto) octadodecanoate (oxLig-2), are ligands for beta2-GPI (J Lipid Re 2001; 42: 697; J Lipid Res 2002; 43: 1486). These beta2-GPI ligands provide an electrostatic interaction between oxLDL and beta2-GPI followed by forming stable complexes (such as Schiff base adducts). The omega-carboxyl function in these ligand is responsible for beta2-GPI binding to oxLDL and the oxLDL-beta2-GPI complexes are anti-beta2-GPI auto-Ab-dependently taken up by macrophages (i.e., by phagocytosis). Our recent observations are consistent with the evidence that beta2-GPI co-localizes with lymphocytes and mononuclear cells in human athero-plaques. Thus, autoimmune thrombogenesis (atherogenesis) is linked to interaction of anti-beta2-GPI Abs with the beta2-GPI-oxLDL complexes. We propose an alternative idea, that an immune response against the beta2-GPI-oxLDL complexes may be involved in mechanisms in the development of atherosclerosis, which has been explained by the theory of 'the response to injury'.
Lupus 2003
PMID:Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome. 1289 97

The CD40-CD40L system has pleiotropic effects in a variety of cells and biological processes including immune response, thrombosis and atherogenesis. Within the immune system, these molecules represent a critical link between its humoral and cellular arms. As a result of these attributes and based on preclinical data in animals, anti-CD40L antibodies were tested in a variety of immunologic diseases including idiopathic thrombocytopenic purpura, psoriasis, Crohn's disease, systemic lupus erythematosus and transplantation. Phase I/II studies in humans with lupus nephritis demonstrated reduction of anti-double-stranded DNA (anti-dsDNA) antibodies but not of protective antibodies. Reduction of anti-DNA was associated with increased serum complement levels and reduced glomerular inflammation. As a result of thrombotic effects, observed even in patients negative for anti-cardiolipin antibodies, there is a temporary halt on further human studies. The reasons for the prothrombotic effects are not clear at present but may represent effects on platelets and/or the endothelium. In view of the significant immunomodulatory effects of anti-CD40L treatment in patients with lupus nephritis, the increasing realization of the importance of premature atherosclerosis in lupus and an increasing amount of data supporting a role for the CD40-CD40L interactions in this process, inhibition of this pathway deserves further exploration in lupus.
Lupus 2004
PMID:Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients. 1523 Feb 98

There is limited knowledge of potential defects in arterial wall properties in female systemic lupus erythematosus (SLE) patients without manifest cardiovascular disease (CVD) and significant atherosclerotic lesions. The aim of the present study was to investigate the mechanical properties of larger vessels in these patients and to compare them with healthy controls. B-mode ultrasound was used to assess vessel wall structure and to exclude presence of plaque. The ankle/brachial pressure index was measured to exclude occlusive arterial disease. An ultrasound echo-tracking system was used to determine stiffness of the abdominal aorta, common carotid artery (CCA) and popliteal artery (PA) in 39 female patients with SLE and 55 female, healthy controls. SLE had an independent effect on stiffening of the CCA (P = 0.01) and PA (P = 0.005). In addition, larger vessel diameters were observed in the CCA (P = 0.002) after adjustments for the effects of mean arterial pressure and age. Thus, this investigation demonstrated an increased arterial stiffness and signs of premature vascular ageing in the SLE patients without manifest cardiovascular disease and without significant atherosclerotic lesions. The results of this study indicate that other mechanisms besides atherosclerosis might be involved in the pathogenesis of arterial stiffening in SLE patients.
Lupus 2004
PMID:Abnormal mechanical properties of larger arteries in postmenopausal women with systemic lupus erythematosus. 1564 46

The objective of the study was to determine the clinical differences at diagnosis and during follow-up between male and female patients with primary antiphospholipid syndrome (PAPS). We analysed 68 patients, 30 males and 38 females diagnosed and followed between 1990 and 2003. Patients with antiphospholipid syndrome associated with systemic lupus erythematosus at onset and during follow-up were excluded. The mean age at diagnosis was 31.4 +/- 11 years in males and 35.7 +/- 11 years in females (NS). The follow-up after diagnosis was 8.7 +/- 3.1 years in males and 9.2 +/- 2.9 years in females (NS). We did not find significant differences between the two groups with respect to venous and arterial thrombosis. However, in female patients, stroke was more prevalent than in male patients (12/38 versus 3/30, P = 0.03). In contrast, we found a significant prevalence of severe gastrointestinal complications in male compared to female patients (7/30 versus 1/38, P = 0.009). One male patient died due to catastrophic antiphospholipid syndrome. This study suggests that clinical course in patients with PAPS may be different with significant prevalence of central nervous system involvement in females and gastrointestinal involvement in males. Factors such as accelerated atherosclerosis, hormones, related to gender could be the explanation of these findings.
Lupus 2005
PMID:The impact of gender on clinical manifestations of primary antiphospholipid syndrome. 1617 32

Heart damage, mediated by different autoantibodies can involve several anatomical heart structures: valves, arteries, conduction tissue. Verrucous endocarditis is frequently reported in patients with antiphospholipid syndrome (APS) with or without systemic lupus erythematosus (SLE), particularly if they suffer from central nervous system involvement. Antiphospholipid antibodies (aPL) were shown deposited at subendothelial level of the affected valves. According to several in vitro and in vivo experimental models, aPL, anti-oxidized LDL (oxLDL), anti-heat shock protein 65 (HSP65) and anti-endothelial cells antibodies (AECA) seem to be involved in the pathogenesis of the atherosclerosis phenomena described in systemic autoimmune disease and vasculitis. However, the observation of the association of the same antibodies with clinical and subclinical atherosclerosis in patients is still controversial. The children of anti-Ro/SSA positive mothers can be affected by the congenital heart block. Anti Ro/SS-A antibodies play a major pathogenic role in affecting the heart conduction tissue in this rare condition.
Lupus 2005
PMID:Nonorgan specific autoantibodies and heart damage. 1621 61

The role of the immune system in modulating atherosclerosis has recently been well documented. Studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic plaque formation. This includes macrophages, CD4+ T cells and dendritic cells as well as autoantigens such as oxidized low density lipoprotein (oxLDL), heat shock proteins and beta2-glycoprotein I. Given these recent advances, various modifications of the immune system in experimental models have been proposed as therapeutic strategies, with the potential of inhibiting atherosclerosis progression. These modifications are switching the immune system (CD4+ T cells) from Th1 towards a Th2 anti-inflammatory cytokine secretion, and the induction of protective antibodies both of which may be induced by specific vaccination. Recent identification of specific immunoreactive antigenic epitopes on modified LDL, their successful implementation for immunization and the induction of atheroprotection, supports the idea that active vaccination may emerge as a novel immuno-modulating atheroprotective strategy.
Lupus 2005
PMID:Predictive and protective autoimmunity in cardiovascular diseases: is vaccination therapy a reality? 1621 63

Systemic inflammatory/autoimmune rheumatic diseases are associated with a significantly increased rate of atherosclerosis and cardiovascular disease. Several mechanisms of accelerated atherosclerosis have been proposed, including abnormal lipid and lipoprotein profiles, oxidative stress, enhanced apoptosis, thrombophilia, immune complexes and increased mononuclear cell infiltration of atherosclerotic lesions, local generation of cytokines and female estrogen deficiency. However, the widely shared enthusiasm about the cardioprotective potential of hormone replacement therapy (HRT) with estrogens, has come to an abrupt halt since very recent randomized trials failed to show a cardiovascular risk reduction in postmenopausal women. Several factors might play a role in these discrepancies, in particular, parts of the striking discrepancy between observational and randomized data have been attributed to an estrogen-mediated adverse effect on inflammation (enhancement, possibly dose-related). In fact, estrogens potentially increase the inflammatory/immune response in autoimmune rheumatic diseases. New roles for estrogen peripheral metabolites (hydroxylated) and their increased formation in inflammatory sites, might partially introduce some explanations for several apparently contrasting evidences.
Lupus 2005
PMID:Estrogens, autoimmunity and the heart. 1621 65

Cardiovascular (CV) disease morbidity and mortality are increased in patients with rheumatoid arthritis (RA) and much of the excess CV disease morbidity appears to be due to atherosclerosis. The pathogenesis of atherosclerosis (ATS) in RA is complex and there is increasing evidence that many factors including novel and traditional cardiovascular risk factors, RA treatments and the RA inflammatory disease process are involved in the development of CV disease in these patients. Of particular interest are the effects of chronic inflammation and immune dysregulation associated with RA. These have been shown to be associated with endothelial dysfunction, which is an early, potentially reversible, functional abnormality of the arterial wall. However, as several CV disease risk factors and drug prescribing are also influenced by RA disease severity it is very difficult to separate out the effects of the inflammatory disease burden on the cardiovascular system in RA.
Lupus 2005
PMID:Cardiovascular involvement in rheumatoid arthritis. 1621 66

Pericarditis is the most common cardiac abnormality in systemic lupus erythematosus (SLE) patients, but lesions of the valves, myocardium and coronary vessels may all occur. In the past, cardiac manifestations were severe and life threatening, often leading to death. Therefore, they were frequently found in post-mortem examinations. Nowadays cardiac manifestations are often mild and asymptomatic. However, they can be frequently recognized by echocardiography and other noninvasive tests. Echocardiography is a sensitive and specific technique in detecting cardiac abnormalities, particularly mild pericarditis, valvular lesions and myocardial dysfunction. Therefore, echocardiography should be performed periodically in SLE patients. Vascular occlusion, including coronary arteries, may develop due to vasculitis, premature atherosclerosis or antiphospholipid antibodies associated with SLE. Premature atherosclerosis is the most frequent cause of coronary artery disease (CAD) in SLE patients. Efforts should be made to control traditional risk factors as well as all other factors which could contribute to atherosclerotic plaque development.
Lupus 2005
PMID:Cardiac involvement in systemic lupus erythematosus. 1621 67


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