Phospholipase A(2) in vascular disease

Secretory phospholipase A(2) (PLA(2)) Can be proatherogenic both in the cir culation and in the arterial wall. In blood plasma, PLA(2) can modify the c irculating lipoproteins and so induce formation of small dense LDL particle s, which are associated with increased risk for cardiovascular disease. In the arterial wall, PLA(2) can hydrolyze lipoproteins. The PLA(2)-modified l ipoproteins bind tightly to extracellular proteoglycans, which may lead to their enhanced retention in the arterial wall. The modified lipoproteins ma y also aggregate and fuse, which can lead to accumulation of their lipids w ithin the extracellular matrix. The PLA(2)-modified particles are more susc eptible to further modifications by other enzymes and agents and can be tak en up by macrophages, leading to accumulation of intracellular lipids. In a ddition, lysophospholipids and free fatty acids, the hydrolysis products of PLA(2), promote atherogenesis. Thus, these lipid mediators can be carried, either by the PLA(2)-modified lipoproteins themselves or by albumin, into the arterial cells, which then undergo functional alterations. This may, in turn, lead to specific changes in the extracellular matrix, which increase the retention and accumulation of lipoproteins within the matrix. In the p resent article, we discuss the possible actions of PLA(2) enzymes, especial ly PLA(2)-IIA, in the arterial wall during atherogenesis.