Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral artery disease (PAD) is mostly related to atherosclerosis. Autoimmunity and, in particular, antibodies to cardiolipin (aCL) and phospholipid cofactors such as beta2-glycoprotein I (beta2-gpI) might influence the development of atheroma. Beta2-glycoprotein I (beta2-gpI) has been found in atheroma. It has previously been shown that immunoglobulin A (IgA) anti-beta2-gpI antibodies are associated with a risk of cerebral ischemia and myocardial infarction. This case control study aimed to determine whether elevated levels of aCL/anti-beta2-gpI antibodies are associated with a risk of symptomatic PAD (sPAD). Cases comprised a nonselected population of patients with sPAD (intermittent claudication or critical ischemia). Patient recruitment was based on arteriography changes. Controls were selected from patients admitted to orthopedic wards as a result of fractures or muscle-ligamentous disorders. Age, sex, race, hypertension, smoking, diabetes mellitus, and hypercholesterolemia were evaluated as risk factors in both groups. IgG/IgM/IgA aCL and anti-beta2-gpI were detected by enzyme-linked immunoabsorbant assays (ELISA). To estimate the grade of association of antibodies with sPAD, odds ratios (OR) were calculated. Logistic regression was utilized for adjustment of confounding factors. Seventy-seven cases and 93 controls were studied. The mean age was 61.5 years for cases and 47.5 years for controls (p <0.001). Among the risk factors evaluated, the presence of hypertension showed the strongest association with sPAD (OR 12.1; 95%CI 5.8-30). The presence of IgA anti-beta2-gpI was independently associated with sPAD (OR 5.4; 95%CI 1.8-15.8; p = 0.01). IgA aCL was strongly associated with the outcome (nonadjusted OR 11.5 after Agresti correction). IgA aCL and IgA anti-beta2-gpI antibodies were not associated with any known risk factors for sPAD or with arteriography changes. The occurrence of these autoantibodies might represent one of the links between autoimmunity and atherosclerosis in patients with sPAD.
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PMID:Autoantibodies to the atheroma component beta2-glycoprotein I and risk of symptomatic peripheral artery disease. 1762 83

The immunolocalization of oxidized low-density lipoproteins (ox-LDL), beta2-glycoprotein I (beta(2)GPI), CD4(+)/CD8(+) immunoreactive lymphocytes, and immunoglobulins in atherosclerotic lesions strongly suggested an active participation of the immune system in atherogenesis. Oxidative stress leading to ox-LDL production is thought to play a central role in both the initiation and progression of atherosclerosis. ox-LDL is highly proinflammatory and chemotactic for macrophage/monocyte and immune cells. Enzyme-linked immunosorbent assays (ELISAs) to measure circulating ox-LDL have been developed and are being currently used to assess oxidative stress as risk factor or marker of atherosclerotic disease. ox-LDL interacts with beta(2)GPI and circulating ox-LDL/beta(2)GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It has been postulated that beta(2)GPI binds ox-LDL to neutralize its proinflammatory and proatherosclerotic effects. Because beta(2)GPI is ubiquitous in plasma, its interaction with ox-LDL may mask oxidized epitopes recognized by capture antibodies potentially interfering with immunoassays results. The measurement of ox-LDL/beta(2)GPI complexes may circumvent this interference representing a more physiological and accurate way of measuring ox-LDL.
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PMID:Determination of oxidized low-density lipoproteins (ox-LDL) versus ox-LDL/beta2GPI complexes for the assessment of autoimmune-mediated atherosclerosis. 1778 19

Macrophage uptake of oxidized LDL (oxLDL) plays a critical role in early stages of atherosclerosis. We previously reported that oxLDL forms stable complexes with beta2-glycoprotein I (beta2GPI), and that these complexes were frequently present in the sera of patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). oxLDL/beta2GPI complexes were shown to be antigenic targets for autoantibodies present in APS. To understand the role of autoantibodies in accelerated atherosclerosis of SLE and APS, we investigated the binding characteristics of beta2GPI and oxLDL to mouse macrophages, and the effect of anti-beta2GPI and anti-oxLDL autoantibodies on this macrophage binding. IgM anti-oxLDL antibody (derived from Apoe -/- mouse) showed inhibitory effect on oxLDL binding to macrophages. Although beta2GPI partly inhibited oxLDL binding to macrophages, IgG anti-beta2GPI autoantibody (derived from APS model mouse) showed pro-atherogenic property by promoting the binding of oxLDL/beta2GPI to macrophages.
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PMID:Atherogenic antiphospholipid antibodies in antiphospholipid syndrome. 1789 14

Abnormal increases of antiphospholipid antibody and plasma homocysteine levels are recently emerging as nonlipidic risk factors for cerebral atherogenesis and thrombosis. Both antiphospholipid antibody and homocysteine share many similar bioeffects in hemostasis, but their interaction is still inconsistent. In this study, we examined the relation between the plasma homocysteine level and lupus anticoagulant, anticardiolipin antibody, and anti-beta2-glycoprotein I antibody in patients with noncardiac cerebral ischemia. Systemic lupus erythrematosus patients were excluded. The results showed a higher frequency of moderate hyperhomocysteinemia in patients with an abnormal increase of lupus anticoagulant only. Neither the serum folate and cobalamin levels nor methylenetetrahydrofolate reductase allele mutation contributes to this result. Accordingly, homocysteine interacts with lupus anticoagulant to promote cerebral atherosclerosis and ischemia. The role of vasculopathic or prothrombotic autoantibody generation in response to specific pathological change such as hyperhomocysteinemia warrants further investigation.
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PMID:Hyperhomocysteinemia relates to the subtype of antiphospholipid antibodies in non-SLE patients. 1791 Nov 91

Atherosclerosis (AT) is a metabolic, systemic inflammatory/immune disease characterized by lipoproteins metabolism alteration that leads to immune/inflammatory system activation with the consequent proliferation of smooth-muscle cells, narrowing arteries and atheroma formation. Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombophilic state and circulating antiphospholipid antibodies (aPL) including anti beta2-GPI. Experimental studies and human observations suggest that APS is associated with AT. In fact, innate and adaptive immune responses participate in the pathogenesis of both diseases. Anti-oxLDL, anti-aPL, anti beta2GPI, anti-HSP antibodies, among others, has been found in patients with APS and AT. Endothelial dysfunctions, oxidative stress, increase of cell adhesion molecules, active platelets, are common findings in both diseases. Macrophages, dendritic cells, T-cell activation, CD40-CD40 ligand interaction, are considered as pathogenic mechanism of AT and APS. Premature AT may be the first symptom of APS. Thrombophilia, aPL antibodies, and APS may be present in patients with premature AT. An association between AT and venous thrombosis (a clinical hallmark of APS) has been proposed in unselected patients with deep venous thrombosis of the legs without symptomatic AT. Asymptomatic AT, defined in terms of carotid intima media thickness and lumen diameter decrease, was observed in patients with APS. Premenopausal female patients with PAPS have a higher prevalence of cerebrovascular disease in comparison with male patients. Accelerated AT and hormones could be the explanation of these findings. High levels of aCLs, significantly predict the risk of future ischemic stroke in women but not in men. AT is one of the main features of systemic APS and offer opportunities for new treatment strategies.
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PMID:Systemic antiphospholipid syndrome and atherosclerosis. 1791 89

Anti-oxidised low-density lipoprotein (anti-oxLDL) antibodies are a heterogeneous group of autoantibodies including both pathogenic and protective subsets. Whereas in most studies the levels of anti-oxLDL antibodies were associated with enhanced atherosclerosis as evaluated by different methods, immunization with oxLDL leads to elevated levels of anti-oxLDL and protection against atherosclerosis. Anti-oxLDL can also be used for immunomodulation of atherosclerosis (i.e. possible therapeutic use of intravenous immunoglobulin, oral tolerance). More specific autoantibodies out of total anti-oxLDL should be selected, for instance, anti-oxLDL/beta-2-glycoprotein I complex, hence defining the fine-tuning of anti-oxLDL antibodies might detect which autoantibodies are pathogenic and which can be used therapeutically.
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PMID:The fine-tuning of anti-oxidized low-density lipoprotein antibodies in cardiovascular disease and thrombosis. 1806 7

It has been reported that IgG to oxidized LDL/beta2-glycoprotein I (oxLDL/beta2GPI) complexes are associated with arterial thromboembolism (TE) in patients with antiphospholipid syndrome (APS). How these antibodies behave in arterial as compared to venous TE in APS is unknown. The aim of the present study was to evaluate the association of IgG anti-oxLDL/beta2GPI with clinical manifestations in category I APS patients. Fifty-seven APS patients with triple positivity (Lupus Anticoagulant (LAC), anti cardiolipin (aCL) and anti-beta2-glycoprotein I (abeta2GPI) antibodies), 28 with arterial and 29 with venous thromboembolism, were included in the study. There were no differences in the dRVVT ratio, IgG/IgM aCL and IgG/IgM abeta2GPI titers in the two patient groups. There were no differences in the IgG (78.5 U+/-59.8 vs. 112.2 U+/-92.3) and IgM (16.3 U+/-15.9 vs. 21.1 U+/-14.3) anti-oxLDL/beta2GPI mean values. A significant correlation was found between IgG anti-oxLDL/beta2GPI and IgG anti-beta2GPI titers in the whole group of APS patients. Patients in the arterial group were older and had more risk factors for atherosclerosis. Data from this study do not support the hypothesis that IgG anti-oxLDL/beta2GPI are specifically associated to arterial TE in Category I APS patients.
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PMID:Antibodies to oxidized LDL/beta2-glycoprotein I in antiphospholipid syndrome patients with venous and arterial thromboembolism. 1832 38

Rheumatoid arthritis (RA) is a systemic inflammatory disease that presents not only involvement of joints but also endothelial dysfunction, dyslipidemia, and premature atherosclerosis. The death rate in RA is known to be higher than in the general population and clinical cardiovascular events secondary to atherosclerosis are responsible for the excessive death rate. A better understanding of the mechanisms that take part in the pathogenesis of atherosclerosis in RA patients is needed. Thus, the authors review the role of several factors involved in RA atherosclerosis, including disease activity, new cardiovascular risk factors, dyslipidemia and the association of atherosclerosis with the use of anti-rheumatic drugs, glucocorticoids and anti-tumor necrosis factor (TNF) agents. The role of humoral autoimmunity, namely autoantibodies against heat shock proteins, cardiolipin and beta2-glycoprotein I, and its link with atherosclerosis is also discussed. It is likely that the elucidation of the key mechanisms of atherogenesis in RA may determine a positive impact by reducing cardiovascular morbidity and mortality of these patients.
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PMID:Multiple factors determine the increased prevalence of atherosclerosis in rheumatoid arthritis. 1834 21

Endothelial dysfunction is considered an important marker in atherosclerosis, having a prognostic value. Antiphospholipid antibodies are considered prothrombotic and have recently been reported to be associated also with atherosclerosis. This study was conducted to investigate a possible association of endothelial dysfunction with various antiphospholipid autoantibodies in healthy subjects and patients with cardiovascular disease. In a single-center, prospective study, 2 groups were included. The study group included patients with cardiovascular diseases (coronary disease and/or cerebrovascular disease) and healthy subjects without apparent heart disease who were referred to the endothelial function laboratory for the assessment of endothelial function. Flow-mediated dilatation, which indicates endothelial function, and nitroglycerin-mediated vasodilatation, which indicates smooth-muscle function, were measured. The 2 groups were evaluated for autoantibodies, including anticardiolipin (aCL; immunoglobulin G [IgG], immunoglobulin M [IgM], and immunoglobulin A [IgA]), antinuclear antibody, anti-beta2-glycoprotein I (IgG, IgM, and IgA), and oxidized low-density lipoprotein. One hundred seven subjects were included in the study: 45 patients (42%) and 62 healthy controls (58%). Flow-mediated dilatation was significantly lower in patients compared with healthy controls (8.0 +/- 9.5% vs 8.0 +/- 13.5%, p = 0.012). In addition, nitroglycerin-mediated vasodilatation was nonsignificantly lower in patients than in healthy controls (8.0 +/- 13.4% vs 11.0 +/- 16.7%, p = 0.084). The mean levels of anti-beta2-glycoprotein I (IgG, IgM, and IgA), aCL (IgM and IgA), antinuclear antibody, and oxidized low-density lipoprotein were not different between groups. However, the mean level of IgG aCL was significantly higher in patients than in healthy controls. In conclusion, in accordance with previous reports of an association between aCL and atherosclerosis, patients with cardiovascular disease had endothelial dysfunction and elevated levels of aCL.
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PMID:Anti-cardiolipin antibodies and endothelial function in patients with coronary artery disease. 1839 39

Although atherosclerosis was previously thought to be mainly a degenerative disease, it is now well ascertained that its pathogenesis is inflammatory. This review describes the history of a new atherogenetic concept, including the pivotal role of apoE-knockout mice in understanding the inflammatory background of atherosclerosis. There has been lack of unequivocal evidence of an important inflammatory component in atherogenesis. This evidence was delivered by a new technique--gene targeting, for the invention of which Mario R. Capecchi, Martin J. Evans and Oliver Smithies received in 2007 the Nobel Prize in Physiology or Medicine. The pivotal stage of atherogenesis is the antigen presentation by macrophages to T lymphocytes. This antigen could be a fragment of oxidized low-density lipoproteins "digested" by macrophage, heat shock protein 60, beta2-glycoprotein I or fragments of bacterial antigens. For interaction between the immunological cells a presence of CD40 receptor on macrophages and its ligand CD40L on the surface of T lymphocytes are necessary. During the interaction between these cells an immunological type T helper 1 (Th1--cellular) or T helper 2 (Th2--humoral) response arises. Th1 response and its mediators: interferon gamma, tumor necrosis factor alpha, interleukin-1, interleukin-12 and interleukin-18 enhance atherogenesis, whereas Th2 response and its mediators: interleukin-4, interleukin-5, interleukin-10 and interleukin-13 inhibit the development of atherosclerosis. Atherosclerosis is therefore a chronic inflammatory disease, in most cases initiated by hypercholesterolemia. Nowadays, hypercholesterolemia and inflammation are considered as "partners in crime". The concept of atherosclerosis as inflammatory disease is fairly new, however, it is already considered as an undisputable achievement of science which have particular therapeutic consequences.
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PMID:New insights into immunological aspects of atherosclerosis. 1847 59


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