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The Role of Lipoprotein-Associated Phospholipase A2 as a Marker and Potential Therapeutic Target in Atherosclerosis

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Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that generates inflammatory mediators within atherosclerotic plaques. In epidemiologic studies there is an association between higher plasma Lp-PLA2 activity and myocardial infarction, stroke and cardiovascular mortality. In animal models, darapladib, a specific inhibitor of Lp-PLA2, decreases the size of the atheroma necrotic core and plaques with thin fibrous caps. Early clinical trials suggest darapladib effectively and safely inhibits Lp-PLA2 activity both in plasma and in carotid atheroma. Two large phase III clinical trials that are currently in progress will determine whether darapladib will reduce the risk of myocardial infarction, stroke, and cardiovascular death by stabilizing atherosclerotic plaques.

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Disclosure

Ralph A.H. Stewart is a member of the Operations Committee of the STABILITY trial. Harvey D. White is a member of the Operations Committee of the STABILITY trial and is also the study’s co-chairman. He has received research grants from Sanofi-Aventis; Eli Lilly; Medicines Company; NIH; Pfizer; Roche; Johnson & Johnson; Schering Plough; Merck Sharpe & Dohme; Astra Zeneca; GlaxoSmithKline; Daiichi Sankyo Pharma Development; and Bristol-Myers Squibb; and a consulting fee from Regado Biosciences.

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  1. Green Lane Cardiovascular Service, Auckland City Hospital, Private Bag 92024, Auckland, 1030, New Zealand

    Ralph A. H. Stewart & Harvey D. White

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  1. Ralph A. H. Stewart
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  2. Harvey D. White
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Correspondence to Ralph A. H. Stewart.

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Stewart, R.A.H., White, H.D. The Role of Lipoprotein-Associated Phospholipase A2 as a Marker and Potential Therapeutic Target in Atherosclerosis. Curr Atheroscler Rep 13, 132–137 (2011). https://doi.org/10.1007/s11883-010-0158-8

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