炎癥已知會(huì)引起氧化壓力和新血管的生長(zhǎng)，而現(xiàn)在,，將這些過程聯(lián)系在一起的一個(gè)分子機(jī)制已被發(fā)現(xiàn)。脂質(zhì)的氧化產(chǎn)物（羧甲基吡咯蛋白加合物）是在發(fā)炎和傷口愈合過程中產(chǎn)生的。這些產(chǎn)物被發(fā)現(xiàn)起Toll-like受體-2(TLR2)的內(nèi)生拮抗劑的作用,，后者通過一個(gè)獨(dú)立于血管內(nèi)皮生長(zhǎng)因子的機(jī)制刺激血管生長(zhǎng)。
這項(xiàng)工作確立了TLR2作為“與氧化相關(guān)的分子模式”的一個(gè)傳感器的新功能,，提供一個(gè)將炎癥,、氧化壓力、先天免疫和血管生成聯(lián)系起來的紐帶,。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
