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STATE-OF-THE-ART PAPER

The CD40/CD40 Ligand System

Linking Inflammation With Atherothrombosis

1st Department of Cardiology, University of Athens Medical School, Athens, Greece

Manuscript received December 30, 2008; revised manuscript received March 5, 2009, accepted March 10, 2009.

^_* Reprint requests and correspondence: Dr. Charalambos Antoniades, 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Ilias 8, Gerakas Attikis, 153 44, Athens, Greece (Email: antoniades{at}vodafone.net.gr).

The role of CD40/CD40 ligand (CD40L) in atherothrombosis is now widely accepted. However, the exact mechanisms linking the CD40/CD40L system and the soluble form of CD40 ligand (sCD40L) with atherothrombosis are currently a topic of intensive research. CD40L and sCD40L belong to the tumor necrosis factor superfamily, and they are molecules with a dual prothrombotic and proinflammatory role. They are expressed in a variety of tissues such as the immune system (in both B and T cells), the vascular wall, and activated platelets. Soluble CD40L has multiple autocrine, paracrine, and endocrine actions, and it may trigger key mechanisms participating in atherothrombosis. CD40/CD40L may participate in the development of coronary atherosclerosis and the triggering of acute coronary syndromes, while sCD40L seems to have a prognostic role not only in subjects with advanced atherosclerosis but also in the general population. Although conventional cardiovascular medication such as antiplatelet therapy, statins, angiotensin-converting enzyme inhibitors, and many others have been shown to reduce both sCD40L and cardiovascular risk, it is still unclear whether specific treatments targeting the CD40/CD40L system will prove to be beneficial against atherothrombosis in the near future.

Key Words: CD40 • CD40L • atherothrombosis • atherogenesis • inflammation • endothelium

Abbreviations and Acronyms   ACS = acute coronary syndrome   AMI = acute myocardial infarction   CAD = coronary artery disease   CD40L = CD40 ligand   EC = endothelial cell   GP = glycoprotein   IL = interleukin   sCD40L = soluble CD40 ligand   SMC = smooth muscle cell

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