Phospholipase A(2) and small, dense low-density lipoprotein

High levels of small, dense LDL in plasma are associated with increased ris k for cardiovascular disease. There are some biochemical characteristics th at may render small, dense LDL particles more atherogenic than larger, buoy ant LDL particles. First, small, dense LDL particles contain less phospholi pids and unesterified cholesterol in their surface monolayer than do large, buoyant LDL particles. This difference in lipid content appears to induce changes in the conformation of apolipoprotein B-100, leading to more exposu re of proteoglycan-binding regions. This may be one reason for the high-aff inity binding of small, dense LDL to arterial proteoglycans. Reduction of t he phospholipid content in the surface monolayer LDL by treatment with secr etory phospholipase A(2) (sPLA(2)) forms small, dense LDL with an enhanced tendency to interact with proteoglycans. circulating levels of sPLA(2)-IIA appears to be an independent risk factor for coronary artery disease and a predictor of cardiovascular events. In addition, in-vivo studies support th e hypothesis that sPLA(2) proteins contribute to atherogenesis and its clin ical consequences. These data suggest that modification of LDL by sPLA(2) i n the arterial tissue or in plasma may be a mechanism for the generation of atherogenic lipoprotein particles in vivo, with a high tendency to be entr apped in the arterial extracellular matrix. Curr Opin Lipidol 11:465-471. ( C) 2000 Lippincott Williams & Wilkins.