title: Recent developments with lipoprotein-associated phospholipase A2 inhibitors.
abstract: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a calcium-independent phospholipase A(2) enzyme secreted by leukocytes and associated with circulating low-density lipoprotein and macrophages in atherosclerotic plaques. Until recently, the biological role of Lp-PLA(2) in atherosclerosis was controversial, but now the preponderance of evidence demonstrates a proatherogenic role of this enzyme. Lp-PLA(2) generates two proinflammatory mediators, lysophosphatidylcholine and oxidized nonesterified fatty acids, which play a major role in the development of atherosclerotic lesions and formation of a necrotic core, leading to more vulnerable plaques. These findings have opened the door to a potential novel therapeutic target, selective inhibition of Lp-LPA(2). Recently, both animal models and human studies have shown that selective inhibition of Lp-PLA(2) reduces plasma Lp-PLA(2) activity, plaque area, and necrotic core area. This article reviews the most recent developments with Lp-PLA(2) inhibitors.
authors.affiliation: Pennsylvania Hospital, 1 Pine West, 800 Spruce Street, Philadelphia, PA 19107, USA. chauffer@uphs.upenn.edu
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Chauffe
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wilensky
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors* / Q000097:blood; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D015507:Drugs, Investigational; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008264:Macrophages / Q000201:enzymology; D009203:Myocardial Infarction / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015507:Drugs, Investigational; D008077:Lipoproteins, LDL; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase