title: Secreted phospholipase A2, lipoprotein hydrolysis, and atherosclerosis: integration with lipidomics.
abstract: Phospholipase A(2) (PLA(2)) is a group of enzymes that hydrolyze the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. Of many PLA(2)s or related enzymes identified to date, secreted PLA(2)s (sPLA(2)s) comprise the largest family that contains 10 catalytically active isozymes. Besides arachidonic acid released from cellular membranes for eicosanoid synthesis, several if not all sPLA(2)s have recently been implicated in hydrolysis of phospholipids in lipoprotein particles. The sPLA(2)-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 sPLA(2)s leads to development of atherosclerosis in mice. More importantly, genetic deletion or pharmacological inhibition of particular sPLA(2)s significantly attenuates atherosclerosis and aneurysm. In this article, we will give an overview of current understanding of the role of sPLA(2)s in atherosclerosis, with recent lipidomics data showing the action of a subset of sPLA(2)s on lipoprotein phospholipids.
authors: Lipid Metabolism Project, The Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors: Kei
authors: K
authors: Yamamoto
authors: Yuki
authors: Y
authors: Isogai
authors: Hiroyasu
authors: H
authors: Sato
authors: Yoshitaka
authors: Y
authors: Taketomi
authors: Makoto
authors: M
authors: Murakami
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008055:Lipids / Q000032:analysis*; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice; D054497:Phospholipases A2, Secretory / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D008055:Lipids; D008074:Lipoproteins; D054497:Phospholipases A2, Secretory