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 A(2) (Lp-PLA(2)) in atherosclerosis, partly because of the lack of simple animal models with a human-like pattern of Lp-PLA(2) 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-PLA(2) might play an important role in plaque vulnerability. As a result, additional studies are warranted to determine whether Lp-PLA(2) inhibition improves plaque stability and ultimately clinical outcomes for high-risk patients.