Secreted phospholipase A2, lipoprotein hydrolysis,and atherosclerosis: integration with lipidomics

Phospholipase A₂ (PLA₂) is a group of enzymes that hydrolyze the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. Of many PLA₂s or related enzymes identified to date, secreted PLA₂s (sPLA₂s) comprise the largest family that contains 10 catalytically active isozymes. Besides arachidonic acid released from cellular membranes for eicosanoid synthesis, several if not all sPLA₂s have recently been implicated in hydrolysis of phospholipids in lipoprotein particles. The sPLA₂-processed low-density lipoprotein (LDL) particles contain a large amount of lysophospholipids and exhibit the property of “small-dense” or “modified” LDL, which facilitates foam cell formation from macrophages. Transgenic overexpression of these sPLA₂s leads to development of atherosclerosis in mice. More importantly, genetic deletion or pharmacological inhibition of particular sPLA₂s significantly attenuates atherosclerosis and aneurysm. In this article, we will give an overview of current understanding of the role of sPLA₂s in atherosclerosis, with recent lipidomics data showing the action of a subset of sPLA₂s on lipoprotein phospholipids.