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lüll Recent developments with lipoprotein-associated phospholipase A2 inhibitors Chauffe RJ; Wilensky RL; Mohler ER 3rdCurr Atheroscler Rep 2010[Jan]; 12 (1): 43-7Lipoprotein-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.|*Drugs, Investigational[MESH]|1-Alkyl-2-acetylglycerophosphocholine Esterase/*antagonists & inhibitors/blood[MESH]|Atherosclerosis/complications/*drug therapy/enzymology[MESH]|Humans[MESH]|Leukocytes/enzymology[MESH]|Lipoproteins, LDL/blood/drug effects[MESH]|Macrophages/enzymology[MESH]|Myocardial Infarction/enzymology/etiology/*prevention & control[MESH]|Risk Factors[MESH]|Treatment Outcome[MESH] |