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.

journal_name

Curr Atheroscler Rep

authors

Chauffe RJ,Wilensky RL,Mohler ER 3rd

doi

10.1007/s11883-009-0076-9

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

43-7

issue

1

eissn

1523-3804

issn

1534-6242

journal_volume

12

pub_type

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