Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development (Nat Med, 2008, 14:1059-1066)

報告日期: 2009/04/28
報告時間: 16:05/16:55
報告學生: 莊智弘
講評老師: 蔡曜聲
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980428-2.pdf

Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development

.

Nat Med. 2008 Oct;14(10):1059-66.

 

Speaker: Chuang Chih-Hing (莊智弘)

Commentator: Tsai, Yau-Sheng, Ph.D (蔡曜聲老師)

Date: 2008/04/28 16:10-17:00

Place Room: 602

 

Abstract:

 

Atherosclerosis is a progressive disease of the arteries and is the primary cause of heart attacks and strokes. The atherosclerotic process is initiated when low-density lipoprotein cholesterol (LDL; the ‘bad’ cholesterol) accumulates in the artery1. Lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor acetylhydrolase or type VIIA PLA2, is a calcium-independent phospholipase A2. In humans, Lp-PLA2 is secreted by leukocytes and is associated with circulating LDL and macrophages in atherosclerotic plaques2. Here the author show that selective inhibition of Lp-PLA2 with darapladib reduced development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic swine. Darapladib markedly inhibited plasma and lesion Lp-PLA2 activity and reduced lesion lysophosphatidylcholine content. Analysis of coronary gene expression showed that darapladib exerted a general anti-inflammatory action, substantially reducing the expression of 24 genes associated with macrophage and T lymphocyte functioning. Darapladib (Lp-PLA2 inhibitor) treatment resulted in a considerable decrease in plaque area and, notably, a markedly reduced necrotic core area and reduced medial destruction, resulting in fewer lesions with an unstable phenotype. These data show that selective inhibition of Lp-PLA2 inhibits progression to advanced coronary atherosclerotic lesions and confirms a crucial role of vascular inflammation independent from hypercholesterolemia in the development of lesions implicated in the pathogenesis of myocardial infarction and stroke.

 

Reference:

1.   Glass, C.K. & Witztum, J.L. Cell 104, 503–516 (2001).

2.   Tjoelker, L.W. et al. Nature 374, 549–553 (1995).