炎症已知会引起氧化压力和新血管的生长，而现在，将这些过程联系在一起的一个分子机制已被发现。脂质的氧化产物（羧甲基吡咯蛋白加合物）是在发炎和伤口愈合过程中产生的。这些产物被发现起Toll-like受体-2(TLR2)的内生拮抗剂的作用，后者通过一个独立于血管内皮生长因子的机制刺激血管生长。
这项工作确立了TLR2作为“与氧化相关的分子模式”的一个传感器的新功能，提供一个将炎症、氧化压力、先天免疫和血管生成联系起来的纽带。
生物谷推荐英文摘要：
Nature doi:10.1038/nature09421
Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands
Xiaoxia Z. West1, 2, 4,Nikolay L. Malinin1, 4,Alona A. Merkulova1,Mira Tischenko1,Bethany A. Kerr1,Ernest C. Borden3, Eugene A. Podrez1,Robert G. Salomon2, Tatiana V. Byzova
Reciprocity of inflammation, oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing and remodelling 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 ageing tissues in mice and in highly vascularized tumours in both murine and human melanoma. The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 (TLR2), but not TLR4 or scavenger receptors on endothelial cells, leading to an angiogenic response that is independent of vascular endothelial growth factor. CEP promoted angiogenesis in hindlimb ischaemia and wound healing models through MyD88-dependent TLR2 signalling. Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue revascularization and diminished tumour angiogenesis. Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration. Taken 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.
