We know all about the cell types that gather in atherosclerotic plaques, but not how they communicate with one another to coordinate the progression of the plaque. If we could interrupt the signalling processes that control the immune response, we might be able to halt their development. CD40 seems a likely mediator of the signal for plaque formation, but a role in atherogenesis has yet to be demonstrated in real animals. In the 9 July 1998 issue of Nature , Peter Libby and his colleagues show how they used an antibody to mop up CD40L to reduce the incidence of atherosclerosis in mice. The odds were stacked against the mice.
Cholesterol is a major risk factor for coronary heart disease.
Yet when communication between CD40 and CD40L was prevented, aortic atherosclerotic lesions developed to only half the size of untreated mice, and the lipid content of the plaques was reduced by more than three-quarters. The plaques also contained fewer white blood cells and didn't produce so many adhesion molecules, which help the cells to aggregate. This work presents a hopeful sign that CD40 and CD40L signalling is prominent in atherosclerosis when LDL cholesterol levels are high. Interruption of CD40 signalling therefore presents a promising drug target.