Secretory phospholipase A2: a multifaceted family of proatherogenic enzymes.
Secretory phospholipase A(2) (sPLA(2)) represents a class of enzymes that hydrolyze phospholipids from cellular membranes and lipoproteins, resulting in multifarious proatherogenic actions in the vessel wall. Proatherogenic actions of sPLA(2) involve lipoprotein remodeling that facilitates proteoglycan binding and formation of lipid aggregates that are rapidly internalized by tissue macrophages. The hydrolysis of phospholipids on cell membranes generates bioactive lipids and lipolipoproteins with increased oxidative susceptibility. These particles and other bioactive lipids activate inflammatory pathways in various cells of the vessel wall. Transgenic mice overexpressing groups IIA, V, and X have increased atherosclerosis formation, whereas mice deficient in these sPLA(2) isoenzymes have less atherosclerosis formation. In apolipoprotein E knockout mice fed an atherosclerotic diet, sPLA(2) inhibition with varespladib reduced atherosclerosis formation. The potential for sPLA(2) inhibitors for preventing cardiovascular events is being investigated.
SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 1205, Brooklyn, NY 11203, USA. robert.rosenson@downstate.edu
Robert S
RS
Rosenson
Michael H
MH
Gelb
D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology*; D018450:Disease Progression; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000201:enzymology / Q000503:physiopathology; D007651:Keto Acids; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
D000085:Acetates; D007211:Indoles; D007651:Keto Acids; D008074:Lipoproteins; D010743:Phospholipids; C117948:varespladib; D054497:Phospholipases A2, Secretory