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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In prospective studies antibodies to oxidised LDL (low density lipoprotein) have been shown to predict myocardial infarction and progression of carotid atherosclerosis in non-autoimmune subjects. The antibodies to oxidised LDL are crossreactive with antiphospholipid antibodies most likely due to their binding to oxidised phospholipids. The frequent occurrence of these antibodies and their association with arterial thrombosis in patients with SLE and antiphospholipid syndrome suggest their involvement in the development of accelerated atherosclerosis in these patients. Some in vitro studies suggest that antibodies to oxidised LDL may have an atherogenic effect by enhancing the lipid accumulation into macrophages in the atherosclerotic vessels. These antibodies can be considered as markers of the pathogenic determinants of atherosclerosis, such as enhanced lipid oxidation, proinflammatory stage and impaired vasodilatation.
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PMID:Antibodies to oxidised LDL. 1080 88

The antiphospholipid syndrome(APS) is characterized by predominant clinical features of venous and arterial thrombosis and recurrent pregnancy loss accompanied by antiphospholipid antibodies(aPL) such as anticardiolipin antibodies(aCL) and lupus anticoagulant(LA). In 1990, three individual research groups, including us, first reported that a 50 kD plasma cofactor is required for the binding of aCL to cardiolipin(CL) and now, beta 2-glycoprotein I(beta 2-GPI), which binds to anionic phospholipids(PLs), is widely believed to be the major antigen for aCL. It was also reported that epitopes for such aCL are cryptic and that they appear only when beta 2-GPI interacts with lipid membranes containing anionic PLs, such as CL and phosphatidylserine, or with a polyoxygenated polystyrene surface. In contrast, prothrombin was recently identified as the "true" antigen for LA. In this review paper, we would like to describe on specificity of aPL and also on a possible mechanism on autoantibody-dependent development of atherosclerosis.
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PMID:[Assay principles of antiphospholipid antibodies and heterogeneity of the antibodies]. 1081 Aug 76

The pathogenesis of autoimmune disease is still an enigma. Whereas the diverse clinical manifestations of many autoimmune diseases cannot be explained by the existence of autoantibodies, idiotypic dysregulation may provide an alternative explanation. Experimental models, serum level changes of pathogenic idiotypes during exacerbation and remission, and the increased expression of pathogenic idiotypes following common infections all support this notion. In this article we review experimental models of autoimmune disease induction (systemic lupus erythematosus, antiphospholipid syndrome, Goodpasture's syndrome, autoimmune thyroiditis, and vasculitis) by manipulation of the idiotypic network, and discuss the utilization of idiotypes for the immunotherapy of autoimmune diseases and other conditions that involve the immune system (e.g., atherosclerosis).
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PMID:Idiotypic network dysregulation: a common etiopathogenesis of diverse autoimmune diseases. 1082 56

Animal models of the relatively new antiphospholipid syndrome (APS) enabled researchers to understand disease pathogenesis and to test novel experimental therapeutic modalities. Animal models of APS include spontaneous genetic models and experimental induced models. The latter test more reliably the pathogenicity of antiphospholipid antibodies because the syndrome is induced in normal mice rather than being secondary to a preexisting autoimmune disease. Reports about animal models of APS in the recent year provide new insights into the pathogenesis of antiphospholipid antibodies and beta2-glycoprotein-I in reproductive failure, neurologic manifestations, thrombosis, and atherosclerosis. In addition, novel therapies that were successful in experimental APS included anti-idiotypes, oral tolerance, and specific peptides that bind to beta2-glycoprotein-I. Animal models provide the first step in development of novel therapies for patients with APS.
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PMID:Antiphospholipid syndrome: insights from animal models. 1096 84

Difficulties to establish general characteristics of patients with Raynaud's phenomenon, especially frequency, rates and predisposing factors of the evolution of primary to secondary cases probably originate from substantial variation of evaluated cohorts. We conducted a prospective study using standardised diagnostic procedures in order to look for the specificity of patients referred to the vascular centre; moreover, we assayed anticardiolipin antibodies in these patients using double ELISA and compared its frequency to sex and age matched a control group of 50 healthy individuals. 124 patients (20 men), mean age at onset 35.5 yr, range 9-69 yr, had confirmed diagnosis of Raynaud's phenomenon. Ninety nine patients were found to have secondary phenomenon, 72% of them had trophic changes of fingers and/or toes. Anticardiolipin antibodies assay was positive in seven patients and four healthy donors. Vascular diseases constituted about 20%, and connective tissue diseases 50% of secondary cases, but SLE (17 cases) not a scleroderma (11 cases) was the most frequent clinical entity in the latter group. There were only two patients with Buerger's disease and one with atherosclerosis as an underlying disease for vasospastic disorder. We concluded in the vascular medicine centre that there were a lot of patients with ischemic necrosis or other type of trophic changes, and very little primary, benign Raynaud's disease cases; surprisingly, peripheral arterial occlusive disease was very seldom responsible for vasospastic episodes. Primary or secondary antiphospholipid syndrome is not associated with Raynaud's phenomenon.
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PMID:Clinical spectrum of Raynaud's phenomenon in patients referred to vascular clinic. 1099

beta(2)-glycoprotein I (beta(2)-GPI=apolipoprotein H) is an important autoantigen in patients with the antiphospholipid syndrome. It also plays a role in lipoprotein metabolism, such as anti-atherogenic property, triglyceride removal, and enhancement of lipoprotein lipase. Serum beta(2)-GPI concentration of 812 apparently healthy Japanese individuals was measured by sandwich EIA. Two families with complete beta(2)-GPI deficiency were identified. In one family, all affected had increased serum LDL-cholesterol levels or smaller particle sizes of LDL, while the other had no apparent abnormality in lipid metabolism. Individuals investigated had no history of thrombosis or overt abnormalities in hemostatic tests. A thymine corresponding to position 379 of the beta(2)-GPI cDNA was deleted in every beta(2)-GPI deficient individual. The incidence of this heterozygous deficiency determined by RFLP was 6. 3% in Japanese and none in Caucasians. Heterozygotes had significantly lower concentrations of serum beta(2)-GPI than did those without the mutation, yet no significantly different lipid profiles, such as total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apoA-I, apoB and Lp(a), were observed. A low concentration of beta(2)-GPI seemed not to be associated with apparent abnormality in lipoprotein metabolism.
Atherosclerosis 2000 Oct
PMID:beta(2)-glycoprotein I deficiency: prevalence, genetic background and effects on plasma lipoprotein metabolism and hemostasis. 1099 61

The high correlation between the IgG isotype of anticardiolipin antibodies (aCLs) and clinical thrombosis was first documented in 1983, and this observation was confirmed in subsequent studies. In addition, the frequency of fetal loss and thrombocytopenia was increased in this group of patients. These findings were termed the antiphospholipid syndrome (APS). This syndrome was mostly seen in patients with systemic lupus erythematosus (SLE), but it soon became clear that also other patients not suffering from defined SLE might exhibit features of APS. aCL in APS patients are detected in immunoassays by using solid phase cardiolipin as a putative antigen. However, antibodies directed against phospholipid-binding plasma or serum proteins, beta2-glycoprotein I (beta2-GPI), in particular, are also detected. Many recent studies have indicated that one of predominant antibodies that has been identified as aCL in APS patients is against beta2-GPI rather than any of the negatively charged phospholipids. The epitopes recognized by anti-beta2-GPI antibodies raised in APS patients are composed of discontinuous amino acid sequences from the IV domain of human beta2-GPI. These epitopes are cryptic when beta2-GPI does not interact with anionic phospholipids. An early event in atherosclerosis is the accumulation of cholesterol-laden foam cells, which originate mainly from monocyte-macrophage cells by their uptake of chemically modified low-density lipoprotein (LDL). We found that beta2-GPI binds directly to oxLDL, and that the complex of oxLDL and beta2-GPI is subsequently recognized by aCL (anti-beta2-GPI) to be taken up by macrophages. While the pathogenesis of this accelerated atherosclerosis is likely to be multifactorial, it is possible that antiphospholipid antibodies, including aCL (anti-beta2-GPI antibodies), may have contributed to the formation of atherosclerotic lesion.
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PMID:Antiphospholipid antibodies in arterial thrombosis. 1120 78

Novel risk factors for the progression of atherosclerosis such as C-reactive protein (CRP) and adhesion molecules have stimulated much recent interest in the role of inflammation in atherosclerotic disease. There is also evidence emerging that autoimmunity may have a role in the pathogenesis of atherosclerosis. In this article we explore the evidence for the role of autoimmunity in human atherosclerosis, both in the general population and in the context of the antiphospholipid syndrome. In particular we will focus on several autoantigens, review the evidence for their role in the process of atherosclerosis and the nature of the immune responses.
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PMID:Atherosclerosis and autoimmunity. 1134 Nov

The antiphospholipid syndrome is characterized by arterial and venous thrombosis, as well as pregnancy morbidity, in the presence of elevated levels of antiphospholipid antibodies. These autoantibodies have procoagulant activity, as they affect platelets, humoral coagulation factors, and endothelial cells. In addition, they are proatherogenic, as demonstrated by animal models and by the increased prevalence of cardiovascular diseases in patients with systemic lupus erythematosus and antiphospholipid syndrome. Moreover, antiphospholipid antibodies, including anticardiolipin, anti-b2-glycoprotein-I, and anti-oxidized low-density lipoprotein, are associated with atherosclerosis and its consequences in the general population as well. This autoimmune aspect of atherosclerosis in the presence or absence of an autoimmune disease suggests benefit from development of immunomodulating therapies.
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PMID:Antiphospholipid syndrome, antiphospholipid antibodies, and atherosclerosis. 1138 99

The aim of this study was to examine potential links between antiOxLDL antibodies and the clinical and biological features of secondary antiphospholipid syndrome (II APLS) associated with systemic lupus erythematosus (SLE). A cohort study was done of 98 SLE patients followed-up for 1 y, including 18 with definite II APLS and 13 patients with definite primary APLS (I APLS). IgG anticardiolipin, IgG anti beta2 GPI, lupus anticoagulant, VDRL and IgG antiOxLDL were measured in all 98 study subjects. High antiOxLDL titers were found in seven (39%) of the 18 patients with II APLS vs 10 (12.5%) of the 80 patients without APLS (P < 0.01; OR = 4.45; 95% CI = 1.4-14.1) and none of the 13 patients with I APLS (P < 0.02). The mean antiOxLDL titer was not significantly higher in the SLE patients with than without II APLS (P > 0.05). A high antiOxLDL titer was correlated with deep venous thrombosis (P < 0.01; OR = 5.77; 95% CI = 0.54-61) but not with arterial thrombosis (P > 0.05; OR = 1; 95% CI = 0.29-3.09), thrombocytopenia, central nervous system involvement, livedo reticularis, or a positive Coombs test. The antiOxLDL antibody titer was correlated with the IgG anticardiolipin antibody titer (r = 0.235; P = 0.02) and with the IgG anti-beta2 GPI antibody titer (r = 0.224; P = 0.026). AntiOxLDL elevation was found in 17% of SLE patients and was significantly associated with II APLS and venous thrombosis. We found no evidence suggesting that antiOxLDL may be associated with atherosclerosis.
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PMID:Anti-oxidized low-density-lipoprotein (OxLDL) antibodies in systemic lupus erythematosus with and without antiphospholipid syndrome. 1140 65


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