Lipoprotein-Associated Phospholipase A2: How Effective as a Risk Marker of Cardiovascular Disease and as a Therapeutic Target?

Mohamed      S. Ahmed; Jing      Zhan Ji; Qing      H. Meng

Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been studied extensively in terms of biology, pathophysiology, diagnostic and prognostic values. Lp-PLA2 is an enzyme produced in atherosclerotic plaque by inflammatory cells, linked to LDL, HDL and VLDL. The binding of Lp-PLA2 to a specific lipoprotein fraction renders it more atherogenic. Increasing evidence has demonstrated Lp-PLA2 as a novel “ideal” marker for CVD as of its high specificity for vascular inflammation and low biologic variability. Thus, determination of Lp-PLA2 in individuals may provide clinically relevant information about their future risk of CVD events. In addition, Lp-PLA2 has been considered as a therapeutic target, which has been acted upon indirectly (lipid lowering medications) and directly (Lp-PLA2 antagonists such as darapladib) in pharmacologic therapies. This review will provide an overview on biochemistry, biology, proatherogenic, proinflammatory and proapoptotic effects of Lp-PLA2. Clinical utility and its validity as an independent CVD biomarker as well as a diagnostic biomarker to be detected in the very early stages of atherosclerosis will be also discussed. Moreover, the role of Lp-PLA2 as a pharmacologic therapeutic target is another theme of this review.

Keywords: Lp-PLA2, inflammation, atherosclerosis, biomarker, measurement, therapeutic target, Lipoprotein-associated phospholipase A2, CVD biomarker, Cardiovascular Disease, HDL, VLDL