Mechanisms of Collateral Arteriogenesis in Ishemia

描述（由申请人提供）：本项目的目的是提高我们对缺血性动脉生成的理解。这一过程包括原有小动脉闭塞的向外重塑和新的或“新侧支”的形成，目前还不清楚。此外，许多缺血性疾病患者显示侧支发育缺陷。已经确定了动脉结扎后灌注恢复严重不足的小鼠品系，但损伤的原因尚不清楚。目的我将使用新的方法，我们已经开发的成像动脉生成，将介绍一种新的策略，研究新的侧支形成，并将测试的假设，即新的侧支的形成是有缺陷的应变。有证据表明，形态发生途径，声刺猬缺口，介导的早期血管发育，可能会重新激活在成人损伤和/或重塑。这一途径在动脉形成中的作用尚未研究。我们的初步数据表明Shh信号在侧枝成熟中是重要的。因此，目的II将检查的假设，Shh缺口信号有助于预先存在的侧支成熟和新侧支形成，它是有缺陷的受损菌株。

DESCRIPTION (provided by applicant): The purpose of this project is to improve our understanding of arteriogenesis in ischemia. This process, consisting of outward remodeling of pre-existing arteriole anastomoses and formation of new or "neo-collaterals", is not well understood. Moreover, many patients with ischemic disease show a deficit in collateral development. A mouse strain with a severe deficiency in recovery of perfusion after artery ligation has been identified, but the reasons for the impairment are unknown. Aim I will use new methods we have developed for imaging arteriogenesis, will introduce a new strategy for study of neo-collateral formation, and will test the hypothesis that formation of neo-collaterals is defective in the strain. There is evidence that the morphogenic pathway, Sonic hedgehog-notch, which mediates early vascular development, may be reactivated in adults during injury and/or remodeling. A role for this pathway in arteriogenesis has not been studied. Our preliminary data suggest Shh signaling is important in collateral maturation. Therefore, Aim II will examine the hypothesis that Shh-notch signaling contributes to pre-existing collateral maturation and neo-collateral formation, and that it is defective in the impaired strain.