Novel approaches to ischemic tissue repair

描述（由申请方提供）：在考虑移植或LVAD插入之前，充血性心力衰竭（CHF）患者接受最佳药物治疗，如果左心室功能障碍继发于缺血，则在可行的情况下可以进行血运重建（包括旁路手术和/或经皮介入）。在CHF背景下考虑血运重建的基本原理是基于冬眠心肌的概念，即由于灌注不足而收缩功能低下的存活心肌。我们的实验室一直在追求微血管修复的概念，作为改善缺血性疾病患者症状和功能的一种手段。这些努力包括应用血管生成因子和基于细胞的策略，试图利用自然发生的组织修复机制。本提案是我们实验室先前工作的延伸，也是我们长期目标的延续，即定义缺血组织修复机制并基于这些发现开发新的治疗方法。如果成功的话，这项建议中概述的实验可以确定新的治疗方法，以改善充血性心力衰竭患者的血流和功能。公共卫生相关性：该提案是我们实验室先前工作的延伸，也是我们长期目标的延续，即定义缺血组织修复机制，并确定和开发新的治疗方法，以改善充血性心力衰竭患者的血流和功能。

DESCRIPTION (provided by applicant): Before consideration for transplant or LVAD insertion, patients with congestive heart failure (CHF) are optimized in medical treatment and, if the left ventricular dysfunction is secondary to ischemia, revascularization, consisting of bypass surgery and/or percutaneous intervention, may be performed if feasible. The rationale for considering revascularization in the setting of CHF is based on the concept of hibernating myocardium, i.e. viable myocardium that is hypo-contractile due to hypoperfusion. Our laboratory has been pursuing the concept of microvascular repair as a means of improving symptoms and function in patients with ischemic disease. These efforts have included the application of angiogenic factors and cell based strategies in an attempt to leverage naturally occurring mechanisms for tissue repair. The present proposal is an extension of prior work in our lab and a continuation of our long-standing goal to define mechanisms of ischemic tissue repair and develop novel therapeutics based on these discoveries. If successful the experiments outlined in this proposal could identify novel therapeutics to improve blood flow and function in patients with congestive heart failure. PUBLIC HEALTH RELEVANCE: This proposal is an extension of prior work in our lab and a continuation of our long-standing goal to define mechanisms of ischemic tissue repair and to identify and develop novel therapeutics to improve blood flow and function in patients with congestive heart failure.