Novel approaches to ischemic tissue repair

缺血组织修复的新方法

基本信息

批准号：
7802049
负责人：
DOUGLAS W LOSORDO
金额：
$ 38.13万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-15 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7802049
关键词：
Adult Angiogenic Factor Animals Attenuated Blood capillaries Blood flow Bypass Cardiovascular Diseases Cells Congestive Heart Failure Data Development Disease Embryonic Development Endothelial Cells Erinaceidae Family Functional disorder Gelatinase B Goals Growth Factor Human In Vitro Integral Membrane Protein Intervention Ischemia Knockout Mice Laboratories Left Ventricular Dysfunction Left Ventricular Function MMP9 gene Mediating Medical Modeling Morphogenesis Mus Myocardial Ischemia Myocardium Natural regeneration Operative Surgical Procedures Organ Pathway interactions Patients Pilot Projects Process ROCK1 gene Research Design Rho-associated kinase Role Secondary to Series Signal Transduction Skeletal Muscle Symptoms Testing Tissues Transplantation Up-Regulation Vascular Endothelial Growth Factors Work Wound Healing angiogenesis base capillary cell motility design human SMO protein improved in vitro activity in vivo insight mRNA Expression novel novel strategies novel therapeutics osteopontin overexpression promoter public health relevance repaired research study rho smoothened signaling pathway transcription factor

项目摘要

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.

描述（由申请人提供）：在考虑移植或LVAD插入之前，充血性心力衰竭（CHF）的患者在医疗治疗中进行了优化，如果左心室功能障碍是缺血性的，血运重建，则是旁路手术和/或经皮干预，可能会执行旁路手术和/或经皮干预。在CHF设置中考虑血运重建的基本原理是基于冬眠心肌的概念，即由于灌注不足而导致的可行心肌。我们的实验室一直在追求微血管修复的概念，以改善缺血性疾病患者的症状和功能。这些努力包括应用血管生成因子和基于细胞的策略，以试图利用自然发生的组织修复机制。目前的建议是我们实验室中先前工作的扩展，也是我们长期以来定义缺血组织修复机制的目标的延续，并根据这些发现开发新的治疗剂。如果成功，该提案中概述的实验可以鉴定出新的治疗剂，以改善充血性心力衰竭患者的血液流量和功能。公共卫生相关性：该提案是我们实验室中先前工作的扩展，也是我们长期以来定义缺血组织修复机制，识别和开发新型治疗剂以改善充血性心力衰竭患者的血液流量和功能的持续目标。