The role of lipoprotein-associated phospholipase A2 (Lp-PLA₂) in cardiovascular disease

Lipoprotein-associated Phospholipase A2 (Lp-PLA(2)) is an enzyme that belongs to the A2 Phospholipase superfamily and is produced by inflammatory cells that are involved in the process of atherogenesis. Even though there is controversy in current bibliography whether Lp-PLA(2) exerts proatherogenic or anti-atherogenic properties, the weight of evidence suggests a pro-atherogenic role for this protein. Lp-PLA(2) is detected in human atherosclerotic lesions and elevated Lp-PLA(2) levels are associated with an increased risk of cardiovascular events and adverse events in patients with coronary artery disease independently of traditional risk factors and other markers of inflammation. It has been recently shown that direct pharmacological inhibition of Lp-PLA(2) activity exerts beneficiary effects on the atherosclerotic process. This finding is most interesting since it could offer a novel target for therapeutic intervention in patients suffering from cardiovascular disease. The purpose of this review article is to report on the role of Lp-PLA(2) in cardiovascular diseases and to enlighten the putative pathophysiologic mechanisms by which this protein exerts its effect on cardiovascular function. Additionally, the pharmacological interventions that influence Lp-PLA(2) activity and may offer a new approach for the treatment of atherosclerosis will be analyzed.