Secretory phospholipase: A potential target for cardiovascular therapies

Increasing evidence implicates the activation of inflammatory pathways in the pathogenesis of cardiovascular disease. Accordingly, there is considerable interest in the development of new cardioprotective therapies that target inflammatory factors that promote the progression of heart disease. Secretory phospholipase A₂ (sPLA₂) generates a range of fatty acid and prostaglandin metabolites that play a pivotal role in the molecular events involved in the formation, progression and rupture of atherosclerotic plaque. The findings of sPLA₂ in atherosclerotic plaque, accelerated disease in transgenic models and association between elevated sPLA₂ levels in plasma and adverse cardiovascular events in population studies suggest that the pharmacological inhibition of sPLA₂ may be beneficial. The early experience with the clinical development of sPLA₂ inhibitors to reduce cardiovascular risk will be reviewed.