Angiogeniseis and angiotensin II

由于非肽配体的发现，血管紧张素（Ang） II的受体被分为两个亚型（AT1-R和AT2-R）。AT1-R介导angii的大部分心血管作用。AT2-R在发育中的胎儿中表达水平非常高。它在成人心血管系统中的表达量很低。AT1-R信号刺激HB-EGF释放，激活EGF-R，随后是ERK信号。这种AT1R通路增强了肌细胞或血管平滑肌细胞的VEGF释放，并增强了血管生成反应。在AT1R KO小鼠中，侧支血管形成减少，内皮祖细胞的动员减弱。在AT2R KO小鼠中，atir介导的作用增强，与AT2R的抗atir作用相当。AT2-R激活心血管系统中的激肽/一氧化氮/cGMP系统，导致AT2-R介导的心脏保护、血管舒张和压力尿钠。这些作用由AT2-R传递，主要通过刺激蛋白酪氨酸或丝氨酸/苏氨酸磷酸酶以gi蛋白依赖的方式发挥作用。因此，Ang II通过AT1-R刺激缺血病变血管生成，提示急性心肌梗死Ang II受体阻滞剂可能减弱急性期侧支血流量。

Due to the discovery of nonpeptidic ligands the receptors for angiotensin(Ang) II are classified into two subtypes(AT1-R and AT2-R). AT1-R mediates most of the cardiovascular actions of Ang II. AT2-R is expressed at very high levels in the developing fetus. Its expression is very low in the cardiovascular system of the adult. AT1-R signals stimulate HB-EGF release to activate EGF-R followed by the ERK signaling. This AT1R pathway enhances VEGF releases from myocytes or vascular smooth muscle cells and potenciates angiogenic response. In AT1R KO mice, collateral vessel formation was reduced and mobilization of endothelial progenitor cells was blunted. In AT2R KO mice, ATIR-mediated action was enhanced, comparable with anti-ATIR effect of AT2R. AT2-R activates the kinin/nitric oxide/cGMP system in the cardiovascular systems, resulting in AT2-R-mediated cardioprotection, vasodilation and pressure natriuresis. These effects, transmitted by AT2-R, are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in a Gi-protein-dependent manner. Thus, Ang II stimulates angiogenesis in ischemic lesions via AT1-R, suggesting that in acute myocardial infarction Ang II receptor blocker may attenuate collateral blood flow in acute pahase.