Lipoprotein-associated phospholipase A2: a novel marker of cardiovascular risk and potential therapeutic target.
Although the clinical benefit of statins is well established, these agents reduce the risk of cardiovascular events by only 20 - 40%, and the residual risk for high-risk patients is considerable. The recognition of atherosclerosis as an inflammatory disease has opened the door to numerous complementary therapeutic approaches to further reduce risk and the overall burden of cardiovascular disease. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a novel inflammatory marker of cardiovascular risk that is being evaluated as a potential therapeutic target. The biological function of this enzyme in atherosclerosis has been controversial but recent evidence supports its pro-atherogenic role. The enzyme is predominantly bound to low-density lipoprotein cholesterol particles in humans, and its activity produces bioactive lipid mediators that promote inflammatory processes present at every stage of atherogenesis, from atheroma initiation to plaque destabilisation and rupture. Initial clinical studies suggest that the inhibitors of Lp-PLA(2) can block enzyme activity in plasma and within atherosclerotic plaques. However, more studies are needed to determine the potential clinical benefits of inhibiting Lp-PLA(2).
Macphee
Colin
C
GlaxoSmithKline, Vascular Biology and Thrombosis, 709 Swedeland Road, King of Prussia, PA 19406, USA. colin.h.macphee@gsk.com
Benson
G Martin
GM
Shi
Yi
Y
Zalewski
Andrew
A
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000201:enzymology*; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006801:Humans; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D012307:Risk Factors
D015415:Biomarkers; D004791:Enzyme Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase