Oh Charles C, Klein Jason D, Migrino Raymond Q, Thornburg Kent L
Phoenix Veterans Affairs Health Care System, Phoenix AZ 85022, USA.
Recent Pat Cardiovasc Drug Discov. 2011 Sep;6(3):189-98. doi: 10.2174/157489011797377031.
Recent studies have significantly advanced our understanding of arteriogenesis, raising hope that therapies to increase collateral arterial formation may become important new tools in the treatment of ischemic disease. The most important initiating trigger for arteriogenesis is the marked increase in shear stress which is sensed by the endothelium and leads to characteristic changes. Intracellularly, it was shown that platelet endothelial cell adhesion molecule (PECAM-1) becomes tyrosine-phosphorylated in response to increased shear stress, suggesting a role as a possible mechanoreceptor for dynamic and continual monitoring of shear stress. The signal generated by PECAM-1 leads to the activation of the Rho pathway among others. More than 40 genes have been shown to have a shear stress responsive element. The Rho pathway is activated early and appears to be essential to the arteriogenic response as inhibiting it abolished the effect of fluid shear stress. Overexpression of a Rho pathway member, Actin-binding Rho protein (Abra), led to a 60% increase in collateral perfusion over simple femoral artery occlusion. A patent for the Abra gene has been filed recently. It may be a harbinger of a future where collateral arteries grown on demand may become an effective treatment for ischemic vascular disease.
最近的研究极大地推进了我们对动脉生成的理解，让人燃起希望，即增加侧支动脉形成的疗法可能成为治疗缺血性疾病的重要新工具。动脉生成最重要的起始触发因素是剪切应力的显著增加，这种剪切应力由内皮细胞感知并导致特征性变化。在细胞内，研究表明血小板内皮细胞黏附分子（PECAM-1）会因剪切应力增加而发生酪氨酸磷酸化，这表明它可能作为一种机械感受器，用于动态持续监测剪切应力。PECAM-1产生的信号会导致Rho通路等的激活。已发现超过40个基因具有剪切应力反应元件。Rho通路早期被激活，并且似乎对动脉生成反应至关重要，因为抑制它会消除流体剪切应力的作用。Rho通路成员肌动蛋白结合Rho蛋白（Abra）的过表达导致在单纯股动脉闭塞情况下侧支灌注增加60%。最近已提交Abra基因的专利申请。它可能预示着一个未来，即按需生长的侧支动脉可能成为治疗缺血性血管疾病的有效方法。
