The multi-functionality of CD40L and its receptor CD40 in atherosclerosis

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2009: 102/2 (Aug) pp. 183-420
Pages: 206-214

The multi-functionality of CD40L and its receptor CD40 in atherosclerosis

Dirk Lievens 1; Wouter J. Eijgelaar 1; Erik A. L. Biessen 1; Mat J. A. P. Daemen 1; Esther Lutgens1,2
1 Experimental Vascular Pathology Division (EVP), Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) University of Maastricht, The Netherlands; 2 Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany


Atherosclerosis, inflammation, immunity, co-stimulation, TNF receptor- associated factor


Disrupting the CD40-CD40L co-stimulatory pathway reduces atherosclerosis and induces a stable atherosclerotic plaque phenotype that is low in inflammation and high in fibrosis. Therefore, inhibition of the CD40-CD40L pathway is an attractive therapeutic target to reduce clinical complications of atherosclerosis. The CD40-CD40L dyad is known to interact with other costimulatory molecules, to activate antigen-presenting cells (APC) and to contribute to T-cell priming and B-cell isotype switching. Besides their presence on T-cells and APCs, CD40 and CD40L are also present on macrophages, endothelial cells and vascular smooth muscle cells in the plaque, where they can exert pro-atherogenic functions. Moreover, recent progress indicates the involvement of neutrophil CD40, platelet CD40L and dendritic cell CD40 in atherogenesis. Since systemic CD40-CD40L modulation compromises host defense, more targeted interventions are needed to develop superior treatment strategies for atherosclerosis. We believe that by unravelling the cell-cell CD40-CD40L interactions, inhibition of cell-type specific (signalling components of) CD40(L) that do not compromise the patient’s immune system, will become possible. In this review, we highlight the cell-type specific multi-functionality of CD40-CD40L signalling in atherosclerosis.

You may also be interested in...


P. Matusik (1), B. Guzik (1), C. Weber (2), T. J. Guzik (1)

Thromb Haemost 2012 108 3: 443-456


D. F. J. Ketelhuth (1), G. K. Hansson (1)

Thromb Haemost 2011 106 5: 779-786

Didier Hanriot1,2*, Gaëlle Bello1,2*, Armelle Ropars 1,2, Carole Seguin-Devaux 5, Gaël Poitevin 1,2, Sandrine Grosjean 3, Véronique Latger-Cannard2,3,4, Yvan Devaux 1,2, 5, Faiez Zannad 1,2, Véronique Regnault2,4, Patrick Lacolley 1,2, Paul-Michel Mertes 1,2, Ketsia Hess* 1,2, Dan Longrois*1,2

Thromb Haemost 2008 99 3: 558-569