A model of pericyte-induced EC survival signaling. Endothelial cells and pericytes communicate through the reciprocal exchange of growth factors. PDGF-BB produced by ECs acts to recruit pericytes along growing vascular sprouts. In turn, pericytes confer survival advantage to ECs through PDGF-dependent secretion of vitronectin, (1) which through an integrin αv (2) and NF-κB (3) mediated signaling pathway results in up-regulation of intracrine VEGF-A signaling (4) and Bcl-w expression. (5) Previously described survival factors induced by the paracrine action of pericyte- or tumor cell-derived VEGF-A, such as survivin, Bcl-2, and XIAP, are presumably sensitive to the action of both intra- and extra-cellularly acting VEGFR inhibitors (AG-028262 and sFlt1, respectively), whereas the pericyte-induced autocrine signaling by VEGF-A is only sensitive to intra-cellularly acting inhibitors.
