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

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

Low levels of high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels contribute to the excess rate of cardiovascular events seen in subjects with type 2 diabetes. Fenofibrate treatment partially reverses dyslipidemia in these subjects. However, a paradoxical marked reduction in HDL-C and HDL's major protein, apolipoprotein A-I, is a complication of fenofibrate in combination with rosiglitazone, an insulin-sensitizing agent. Risk factors for this condition, termed hypoalphalipoproteinemia, have yet to be identified. Using a case-control study design with subjects enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we tested the hypothesis that alterations in HDL's protein cargo predispose diabetic subjects to fenofibrate/rosiglitazone-induced hypoalphalipoproteinemia. HDL was isolated from blood obtained from controls (no decreases or increase in HDL-C while receiving fenofibrate/rosiglitazone therapy) and cases (developed hypoalphalipoproteinemia after fenofibrate/rosiglitazone treatment) participating in the ACCORD study before they began fenofibrate/rosiglitazone treatment. HDL proteins were quantified by targeted parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) with isotope dilution. This approach demonstrated marked increases in the relative concentrations of paraoxonase/arylesterase 1 (PON1), apolipoprotein C-II (APOC2), apolipoprotein C-I, and apolipoprotein H in the HDL of subjects who developed hypoalphalipoproteinemia. The case and control subjects did not differ significantly in baseline HDL-C levels or other traditional lipid risk factors. We used orthogonal biochemical techniques to confirm increased levels of PON1 and APOC2. Our observations suggest that an imbalance in HDL proteins predisposes diabetic subjects to develop hypoalphalipoproteinemia on fenofibrate/rosiglitazone therapy.
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PMID:Targeted Proteomics Identifies Paraoxonase/Arylesterase 1 (PON1) and Apolipoprotein Cs as Potential Risk Factors for Hypoalphalipoproteinemia in Diabetic Subjects Treated with Fenofibrate and Rosiglitazone. 2666 75