Lipoprotein modification by secretory phospholipase A(2) enzymes contributes to the initiation and progression of atherosclerosis

Purpose of review Secretory phospholipase A(2)S (sPLA(2)s) are considered to be important enzymes in the initiation and progression of atherosclerosis. In this review, we discuss the various mechanisms by which the direct action of the sPLA(2)S on LDL particles in the arterial intima may contribute to atherogenesis. Recent findings A wealth of evidence, both in vitro and in vivo, supports a role for the sPLA(2)S in atherogenesis. Very recently, systemic inhibition of sPLA(2)S was found to reduce measures of arterial inflammation. The mechanisms behind this inhibition, however, are largely unknown. Here, we discuss the consequences of sPLA(2) action on LDL in the arterial intima and address the recent findings regarding the effects of the lipolytic products of sPLA(2), lysophosphatidylcholine, and fatty acids on intimal cells. LDL modified by sPLA(2) can accumulate in the arterial intima both extracellularly and intracellularly. Importantly, the lipolytic products promote atherosclerosis by monocyte/macrophage recruitment, by enhancing the production of proretentive molecules by vascular smooth muscle cells, and by inducing cell death. Summary Recent findings on sPLA(2)S support the idea that the enzymes contribute to human atherogenesis not only as initiating agents but also in maintaining plaque inflammation.