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Phospholipase A2 inhibition and atherosclerotic vascular disease: prospects for targeting secretory and lipoprotein-associated phospholipase A2 enzymes

Rosenson, Robert S

doi: 10.1097/MOL.0b013e32833eb581
Therapy and clinical trials: Edited by Anton F. Stalenhoef and John J.P. Kastelein

Purpose of review: Selective inhibitors of secretory phospholipase A2 and lipoprotein-associated phospholipase A2 are potential candidates for reducing recurrent cardiovascular events in patients with established coronary heart disease (CHD). With the active enrollment of CHD patients into phase III clinical trials with both classes of inhibitors, this article reviews the available experimental animal and human trial evidence that provides the rationale for the development of the phospholipase A2 inhibitors varespladib methyl and darapladib as preventive therapy.

Recent findings: Recently completed experimental animal studies, human biomarker data, and vascular imaging studies provide support for proceeding with clinical outcome trials secretory phospholipase A2 and lipoprotein-associated phospholipase A2 inhibition.

Summary: Both secretory phospholipase A2 and lipoprotein-associated phospholipase A2 inhibitors hold promise for the reduction of recurrent cardiovascular events in patients treated with current standards of care. The completion of the ongoing clinical event trials has the potential to provide a new dimension to secondary preventive therapy.

Mount Sinai School of Medicine, New York, New York, USA

Correspondence to Robert S. Rosenson, Director, Cardiometabolic Disorders, Professor of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1030, New York, NY 10029, USA E-mail: robert.rosenson@mssm.edu

© 2010 Lippincott Williams & Wilkins, Inc.