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CARDIOLOGY

CD40 Ligand: A Novel Target in the Fight Against Cardiovascular Disease

PharmD Student, Massachusetts College of Pharmacy and Health Sciences, Worcester, MA

Vladimir A Kiyanista

PharmD Student, Massachusetts College of Pharmacy and Health Sciences

Pritesh J Gandhi, PharmD BCPS

Associate Professor of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences; Cardiovascular Pharmacotherapy Specialist, University of Massachusetts Memorial Medical Center, Worcester

Reprints: Pritesh J Gandhi PharmD BCPS, Massachusetts College of Pharmacy and Health Sciences—Worcester, Department of Pharmacy Practice, 19 Foster St., Worcester, MA 01608-1715, fax 508/756-8715, pgandhi{at}mcp.edu

OBJECTIVE: To discuss the role of CD40 ligand (CD40L) in atherosclerosis and acute coronary syndromes (ACS), as well as describe relevant clinical literature evaluating the effects of pharmacotherapeutic agents on CD40L expression and soluble CD40L levels.

DATA SOURCES: A MEDLINE and EMBASE search (1966–September 2003) was conducted using the key terms CD40, CD40 ligand, platelets, inflammation, and drug therapy. Additional primary literature was identified by reviewing the reference lists of relevant original and review papers.

STUDY SELECTION AND DATA EXTRACTION: All articles identified in the search were evaluated, and those deemed relevant were incorporated into the review.

DATA SYNTHESIS: CD40L is a transmembrane protein expressed on T cells, B cells, mast cells, basophils, eosinophils, natural killer cells, macrophages, endothelial cells, vascular smooth muscle cells, and activated platelets. It is also found in plasma as a soluble protein, sCD40L. As a consequence of CD40L binding to its receptor (CD40), several inflammatory processes are initiated. Studies have demonstrated elevated CD40L levels in patients with hypercholesterolemia and ACS, and elevated sCD40L levels have been associated with increased risk of cardiovascular events. Statins, glitazones, glycoprotein IIb/IIIa inhibitors, and clopidogrel have been demonstrated to effectively reduce CD40L levels both in vitro and in vivo. Abciximab has been shown to reduce the occurrence of death or myocardial infarction during 6 months of follow-up in patients with ACS who had the highest levels of sCD40L.

CONCLUSIONS: The proinflammatory and procoagulant protein CD40L represents a novel target in the treatment of atherosclerosis and ACS. A number of therapeutic agents have been shown to modulate the expression of CD40L, findings that could have important clinical applications.

Key Words: CD40, CD40 ligand, inflammation, platelets

Published Online, July 27, 2004. www.theannals.com, DOI 10.1345/aph.1D611

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