Summary. In the early stages of inflammation, the lesion is macrophage-rich and high levels of TNF are expressed. TNF induces proangiogenic, tip cell genes, including VEGFR2, PDGFB, and jagged-1. TNF also blocks VEGFR2 signaling, likely through induction of SHP-1. The ECs are thus primed for sprouting. Once the inflammatory response subsides, inhibition of VEGFR2 signaling is relieved, and VEGF-driven sprouting angiogenesis begins.