The endothelium: an interface between autoimmunity and atherosclerosis in systemic lupus erythematosus?

Area of Science:

• Immunology
• Cardiology
• Rheumatology

Background:

• Patients with systemic lupus erythematosus (SLE) exhibit a higher risk of cardiovascular disease (CVD) than the general population.
• Conventional risk factors do not fully account for the elevated CVD risk in SLE patients.
• Atherosclerosis, a chronic inflammatory condition, is increasingly implicated in SLE-related cardiovascular complications.

Purpose of the Study:

• To review the evidence linking autoantibodies in SLE to the pathogenesis of atherosclerosis and accelerated atherogenesis.
• To explore the mechanisms by which autoantibodies may contribute to endothelial dysfunction and altered lipoprotein metabolism in SLE.
• To discuss the potential role of specific autoantibodies, including anti-oxidized low-density lipoprotein (anti-oxLDL) and antiphospholipid antibodies (aPL), in SLE-associated CVD.

Main Methods:

• Literature review of clinical and in vitro studies investigating autoantibodies in SLE and their association with cardiovascular disease.
• Analysis of the proposed mechanisms of autoantibody-mediated endothelial injury and lipoprotein metabolism alteration.
• Examination of the correlation between autoantibody titres, disease activity, and cardiovascular risk markers in SLE patients.

Main Results:

• Autoantibodies in SLE may promote atherosclerosis by causing endothelial injury and altering lipoprotein metabolism.
• Circulating immune complexes and anti-endothelial cell antibodies can induce a pro-inflammatory endothelial phenotype.
• Antiphospholipid antibodies (aPL) and antibodies to oxidized low-density lipoprotein (anti-oxLDL) have been implicated, though results are conflicting.
• Elevated antibodies to high-density lipoprotein (HDL) and apolipoprotein A1 correlate with coronary ischemia and inversely with paraoxonase activity in SLE patients.

Conclusions:

• Autoantibodies are a potential contributing factor to the accelerated atherogenesis observed in SLE patients.
• Further investigation is warranted to elucidate the precise roles of specific autoantibodies in the pathogenesis of SLE-related cardiovascular disease.
• Understanding these mechanisms may lead to novel therapeutic strategies for CVD prevention in SLE.