Phospholipase A2 as a therapeutic target for atherosclerosis

Among numerous emerging systemic inflammatory biomarkers for atherosclerotic disease and coronary heart disease in particular, experimental and epidemiologic data suggest that enzymes of the superfamily of phospholipase A(2), especially secretory phospholipase A(2) and lipoprotein-associated phospholipase A(2), represent promising candidates. Owing to their ability to hydrolyze the ester bonds of phospholipid molecules, yielding the generation of potent proinflammatory and proatherogenic molecules such as lysophosphatidylcholine and oxidized free fatty acids, lipoprotein-associated phospholipase A(2) and secretory phospholipase A(2) could represent a link between lipid metabolism and inflammatory response, and might be directly involved in atherosclerotic plaque development and progression. Current research focuses on their potential role to aid in risk stratification as a possible surrogate marker of atherosclerosis and, since specific inhibitors of the enzymes are available, on the inhibition of lipoprotein-associated phospholipase A(2) and secretory phospholipase A(2), which may represent a novel strategy to decrease residual risk in patients with a large atherosclerotic burden.