Mechanisms of Collateral Arteriogenesis in Ischemia

描述（由申请人提供）：本项目的目的是提高我们对缺血动脉发生的认识。这一过程包括原有小动脉吻合处的向外重塑和新侧支的形成，目前尚不清楚。此外，许多缺血性疾病患者表现出侧枝发育的缺陷。已发现一种小鼠品系在动脉结扎后灌注恢复严重不足，但其原因尚不清楚。目的：我将使用我们开发的动脉发生成像的新方法，将引入新侧枝形成研究的新策略，并将测试新侧枝形成在菌株中有缺陷的假设。有证据表明，在成人损伤和/或重塑过程中，介导早期血管发育的形态发生通路Sonic hedgehog-notch可能被重新激活。该途径在动脉发生中的作用尚未被研究。我们的初步数据表明Shh信号在侧枝成熟中很重要。因此，Aim II将检验sh -notch信号有助于预先存在的侧枝成熟和新侧枝形成的假设，并且它在受损菌株中是缺陷的。

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.