OxLDL/β2-glycoprotein I complex as a proatherogenic autoantigen. Is atherosclerosis an autoimmune disease?
Abstract
Oxidation of atherogenic low-density lipoproteins (LDL) plays akey role in the pathogenesis of atherosclerosis. Oxidation stress and inflammation are closely interr elated and they can potentiate one another.
In the subendothelial space of the arterial intima, monocytes/macrophages become activated and phagocyte oxidized LDL (oxLDL) via scavenger receptors. It has been demonstrated that oxLDL forms complex with plasma β2-glycoprotein I(β2GPI) and becomes autoantigenic triggering synthesis of specific antiphosholipid antibodies.
It has been documented that oxLDL/β2GPI in immune complex with IgG autoantibody is nternalized by macrophages through the Fcγ receptor. Increased levels of oxLDL/β2GPI were first observed in patients with systemic lupus erythematodes (SLE) and antiphospholipid syndrome (APS), further in individuals with coronary heart disease (CHD) and type 2diabetes mellitus (DM2T).
In aprospective study, initial plasma concentrations of oxLDL/β2GPI correlated with the number and severity of cardiovascular events in patients with chronic CHD over a2-year period.