Atherosclerosis in Patients With Autoimmune Disorders

Abstract

Abstract-Recent findings indicate that presence of activated immune competent cells and inflammation are typical of atherosclerosis, the main cause of cardiovascular disease (CVD). The risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE), and is also raised in other autoimmune diseases such as rheumatoid arthritis. Autoimmunity-related CVD and atherosclerosis are important clinical problems. They may also shed light on interactions between immune reactions and atherosclerosis development and manifestations, not least in women, who have a much higher risk of autoimmune disease than men. In general, a combination of traditional and nontraditional risk factors, including dyslipidemia (and to a varying degree, hypertension, diabetes, and smoking), inflammation, antiphospholipid antibodies (aPLs), and lipid oxidation, contribute to CVD in autoimmune diseases. Premature atherosclerosis is likely to be a major underlying mechanism, although distinctive features, if any, of autoimmunity-related atherosclerosis compared with "normal" atherosclerosis are not clear. One interesting possibility is that factors such as inflammation, neoepitopes on endothelial cells, or aPLs make atherosclerotic lesions in autoimmune disease more prone to rupture than in "normal" atherosclerosis. Some cases of autoimmunity-related CVD may be more related to thrombosis than atherosclerosis. Whether premature atherosclerosis is a general feature of autoimmune diseases such as SLE or only affects a subgroup of patients whereas others do not have an increased risk remains to be demonstrated. Treatment of patients with autoimmune disease should also include CVD aspects and be focused on traditional risk factors as well as on disease-related factors. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation present in atherosclerotic lesions.

Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells

“…Several autoimmune diseases are associated with accelerated atherosclerosis, increased plasma levels of circulating oxLDL, anti oxLDL antibodies, dyslipidemia, and enhanced inflammation (41,42). Some groups have proposed that the immune response to oxidized LDL may be protective with regard to the development of atherosclerosis (43)(44)(45).…”

Atherogenesis and the humoral immune response to modified lipoproteins

“…It has also been proposed that these antibodies may play a pathogenic role in the accelerated atherosclerosis that afflicts patients with SLE and with phospholipid antibodies in general [85,86].…”

“…Other types of phospholipid antibodies react with phosporylcholine (PC) [81] and lysophosphatidylcholine (LPC) [86], formed during LDL oxidation. These antibodies are detected using cardiolipin [89] or commercial preparations of PC complexed with bovine serum albumin [81], and the reaction of patient's sera with this substrate cab be inhibited by oxLDL.…”

TP53 single nucleotide polymorphism (rs1042522) in Iranian patients with coronary artery disease

“…This topic has been widely studied in patients with systemic lupus erythematosus and rheumatoid arthritis (66,67). Furthermore, TP53 also serves a role in autoimmune inflammation, and this may explain the link between the gene and developing CAD (32) Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) is among the known genes involved in autoimmune diseases including type 1 diabetes, celiac disease, rheumatoid arthritis and systemic lupus erythematosus (68,69).…”