Novel approaches to ischemic tissue repair

缺血组织修复的新方法

• 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
• 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

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) 患者应优化医疗治疗，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，包括搭桥手术和/或经皮介入治疗。在 CHF 情况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不足的存活心肌。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。目前的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根据这些发现开发新的治疗方法。如果成功，该提案中概述的实验可以找到新的疗法来改善充血性心力衰竭患者的血流和功能。公共健康相关性：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。