CD40 is a 48-kD glycoprotein which is expressed on the surface of all mature B cells, most mature B-cell malignancies, and on some early B-cell acute lymphocytic leukemias CD40 is not, however, expressed on plasma cells. Evidence is accumulating that point to an active role of immune mediated mechnisms in the development of atheromas. Both humoral and immune mediated responses require the interaction of the CD40 with its ligand, CD40L (CD154 or gp39). Many cells including T cells express both the CD40 and CD40L in human atherosclerotic lesions. Therefore, it has been speculated that T cells mediate many aspects of atherogenesis. The CD40L-CD40 signalling seems to be involved in the experimentally induced autoimmune diseases such as collagen-induced arthritis, lupus nephritis, acute or chronic graft-versus-host disease, multiple sclerosis and thyroiditis. It has been shown that the interruption of the CD40-CD40L interaction can hamper the development of these conditions. Therefore, Mach et al decided to test the hypothesis whether such an interruption would prevent atherogenesis. Mach et al in the July 9th, 1998 issue of Nature provide evidence that the interruption of the CD40-CD40L interaction can prevent atherogenesis. The atherogenesis was induced in mice lacking the receptor for low-density lipoprotein that are fed a high-cholesterol diet for 12 weeks. The interruption of the CD40-CD40L interaction was achieved by treatment of these animals with an antibody against mouse CD40L. This treatment reduced the size of aortic atherosclerotic lesions by 59% and their lipid content by 79%. In addition, this treatment led to a significant reduction of macrophages (64%) and T cells (70%) in the atheromas. Simulatenously, the expression of vascular cell adhesion molecule-1 was reduced. Such data provide evidence for the involvement of immune mediated mechanisms in atherosgenesis and confirm a role for the CD40 signalling during atherogenesis in hyperlipidemic mice. Potentially, such strategy may be used in the prevention of atherosclerosis in humans.

REFERENCE:

Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P: Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 1998 Jul 9;394(6689):200-203

RESOURCES:

Atherosclerosis links
Atherosclerosis: The New York Academy of Science
Atheroscleros is: An overview

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