Role of lipoprotein-associated phospholipase A2 in atherosclerosis and its potential as a therapeutic target.
Despite substantial progress in preventing adverse cardiovascular events with current therapeutic strategies, there remains an extensive residual risk of clinical events, particularly in high-risk patients. Because of the evidence implicating inflammation in the pathogenesis of atherosclerosis, identifying and targeting inflammatory pathways could help further reduce cardiovascular risk. There has been controversy regarding the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) in atherosclerosis, partly because of the lack of simple animal models with a human-like pattern of Lp-PLA2 lipoprotein distribution. However, accumulating evidence from pathology, biology and epidemiology studies favors a pro-atherogenic rather than an atheroprotective role for the enzyme. In particular, Lp-PLA2 might play an important role in plaque vulnerability. As a result, additional studies are warranted to determine whether Lp-PLA2 inhibition improves plaque stability and ultimately clinical outcomes for high-risk patients.
Department of Vascular Biology and Thrombosis, Cardiovascular Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania, USA. colin.h.macphee@gsk.com
Colin H
CH
Macphee
Jeanenne
J
Nelson
Andrew
A
Zalewski
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D050197:Atherosclerosis / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000209:etiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D054467:Phospholipases A2
D004791:Enzyme Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase