Figure 1.

CD40 signaling regulates angiogenesis. (A) CD40-induced signaling pathway in endothelial cells. Interaction of CD40L with CD40 on the surface of endothelial cells results in activation of the Ras signaling pathway. Ras associates with PI3 to induce the expression of VEGF, which in turn stimulates angiogenesis. Platelets are likely to be a major, but not unique, source of CD40L (see The two faces of CD40). (B) Platelets induce neoangiogenesis. Activation of platelets causes them to release a soluble form of CD40L, which can bind CD40 on the surface of endothelial cells. Stimulation of CD40 on endothelial cells activates them and, in a tumor, leads to neovascularization of the tumor. The antiplatelet drug Clopidogrel blocks CD40L secretion by platelets and thereby inhibits neovascularization.