Future Role for Selective Phospholipase A2 Inhibitors in the Prevention of Atherosclerotic Cardiovascular Disease

The high risk of recurrent cardiovascular events even among those receiving standard-of-care therapies established on evidence-based medicine has prompted investigations into novel approaches directed at reducing atherosclerotic burden and improving stability of vulnerable atherosclerotic plaques in an effort to further reduce the risk of cardiovascular events [1]. Members of the phospholipase A(2) superfamily of enzymes serve as potential targets of therapy to reduce cardiovascular events as they are involved in lipoprotein modification, retention and oxidation; and activation of vascular and systemic inflammatory responses [2, 3]. This article will review experimental and human studies with selective phospholipase A2 inhibitors, and discuss the future role for these agents in reducing cardiovascular events. A brief review of specific lipoprotein and inflammatory pathways modulated by secretory phospholipase A(2) (sPLA(2)) enzymes and lipoprotein-associated phospholipase A(2) ( Lp-PLA(2)) will be discussed to foster an understanding regarding their potential role as vascular-specific therapeutic agents.