Reciprocity of inflammation, oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing/remodeling to cancer progression1,2. Whereas the mechanism of hypoxia-driven angiogenesis is well understood3,4, the link between inflammation-induced oxidation and de novo blood vessel growth remains obscure. Here we show that the end products of lipid oxidation, ω-(2-carboxyethyl)pyrrole (CEP) and other related pyrroles5, are generated during inflammation and wound healing and accumulate at high levels in aging tissues and in highly vascularized tumors. The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 (TLR2), but not TLR4 nor scavenger receptors on endothelial cells (ECs), leading to a VEGF-independent angiogenic response. CEP promoted angiogenesis in hind limb ischemia and wound healing models through TLR2 signaling in a MyD88-dependent manner. Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue re-vascularization and diminished tumor angiogenesis. Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration. Together, these findings establish a new function of TLR2 as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.

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