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

Full Abstract

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 co-stimulatory 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.

Author information

Author/s: Lievens, Dirk (D); Eijgelaar, Wouter J (WJ); Biessen, Erik A L (EA); Daemen, Mat J A P (MJ); Lutgens, Esther (E);

Affiliation: Department of Pathology, University of Maastricht, 6229 HX Maastricht, The Netherlands.

Journal and publication information

Publication Type: Journal Article; Review

Journal: Thrombosis and haemostasis (Thromb Haemost), published in Germany. (Language: eng)

Reference: 2009-Aug; vol 102 (issue 2) : pp 206-14

Dates: Created 2009/08/04; Completed 2009/10/21;

PMID: 19652870, status: MEDLINE (last retrieval date: 10/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.