The role of lipoprotein-associated phospholipase a₂ as a marker and potential therapeutic target in atherosclerosis.

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is an enzyme that generates inflammatory mediators within atherosclerotic plaques. In epidemiologic studies there is an association between higher plasma Lp-PLA₂ activity and myocardial infarction, stroke and cardiovascular mortality. In animal models, darapladib, a specific inhibitor of Lp-PLA₂, decreases the size of the atheroma necrotic core and plaques with thin fibrous caps. Early clinical trials suggest darapladib effectively and safely inhibits Lp-PLA₂ activity both in plasma and in carotid atheroma. Two large phase III clinical trials that are currently in progress will determine whether darapladib will reduce the risk of myocardial infarction, stroke, and cardiovascular death by stabilizing atherosclerotic plaques.