Phospholipase A(2) in vascular disease.

Secretory phospholipase A2 (PLA2) can be proatherogenic both in the circulation and in the arterial wall. In blood plasma, PLA2 can modify the circulating lipoproteins and so induce formation of small dense LDL particles, which are associated with increased risk for cardiovascular disease. In the arterial wall, PLA2 can hydrolyze lipoproteins. The PLA2-modified lipoproteins bind tightly to extracellular proteoglycans, which may lead to their enhanced retention in the arterial wall. The modified lipoproteins may also aggregate and fuse, which can lead to accumulation of their lipids within the extracellular matrix. The PLA2-modified particles are more susceptible to further modifications by other enzymes and agents and can be taken up by macrophages, leading to accumulation of intracellular lipids. In addition, lysophospholipids and free fatty acids, the hydrolysis products of PLA2, promote atherogenesis. Thus, these lipid mediators can be carried, either by the PLA2-modified lipoproteins themselves or by ...

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