Human Gene Set: WILENSKY_RESPONSE_TO_DARAPLADIB


Standard name WILENSKY_RESPONSE_TO_DARAPLADIB
Systematic name M18107
Brief description Atherosclerotic process genes whose coronary expression changed after darapladib [PubChem=9939609] treatment.
Full description or abstract Increased lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity is associated with increased risk of cardiac events, but it is not known whether Lp-PLA(2) is a causative agent. Here we show that selective inhibition of Lp-PLA(2) with darapladib reduced development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic swine. Darapladib markedly inhibited plasma and lesion Lp-PLA(2) 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 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-PLA(2) 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18806801   Authors: Wilensky RL,Shi Y,Mohler ER 3rd,Hamamdzic D,Burgert ME,Li J,Postle A,Fenning RS,Bollinger JG,Hoffman BE,Pelchovitz DJ,Yang J,Mirabile RC,Webb CL,Zhang L,Zhang P,Gelb MH,Walker MC,Zalewski A,Macphee CH
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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