RGS 14 Disruption, Vascular Effects Leading to Cardioprotection

RGS 14 破坏、血管效应导致心脏保护

基本信息

批准号：
8888575
负责人：
STEPHEN F VATNER
金额：
$ 62.94万
依托单位：
RBHS-NEW JERSEY MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-10 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8888575
关键词：
Acute Adenylate Cyclase Adhesions Adverse effects Americas Angiogenic Factor Apoptosis Area Atomic Force Microscopy Blood Circulation Blood Vessels Blood flow Cardiac Cardiovascular Diseases Cause of Death Cell Culture Techniques Cell Survival Cells Cessation of life Chronic Cicatrix Coronary Circulation Cyclic AMP Cyclic AMP-Dependent Protein Kinases Data Development Distal Fibrosis GTP-Binding Protein Regulators Genes Grant Growth Factor Guanosine Triphosphate Health Heart Heart Diseases Heart failure Hypertrophy Individual Ischemia Knock-out Knockout Mice Limb structure Longevity MEKs Mediating Modeling Mus Muscle Cells Myocardial Ischemia Nitric Oxide Oxidative Stress Pathway interactions Reperfusion Therapy Risk Role Signal Pathway Signal Transduction Time Tissues Vascular Endothelial Growth Factors Ventricular Remodeling angiogenesis coronary artery occlusion improved in vivo novel protective effect public health relevance receptor

项目摘要

DESCRIPTION (provided by applicant): The role of the regulator of G protein signaling 14 (RGS14) in the heart has never been studied, and we found that the RGS14 KO mice are protected from the adverse effects of acute and chronic ischemia, through angiogenesis/arteriogenesis, which protects from myocardial remodeling and development of heart failure. To accomplish the aims of this proposal, we will examine the following hypotheses: Our first hypothesis is that disruption of RGS14 is a novel mechanism to protect the heart against chronic myocardial ischemia through angiogenesis and arteriogenesis. Our second hypothesis is that the mechanism of acute and chronic ischemic protection involves Gi AC/cAMP and Ras-mediated activation of the MEK/ERK pathway and consequently nitric oxide (NO)/VEGF activation, as well as blocking oxidative stress. A particularly novel feature of the RGS14 Knockout (KO) mouse is its ability to protect against both acute and chronic myocardial ischemia and to induce arteriogenesis/angiogenesis. A second novel feature, that underlies the importance of studying inhibition of a gene with multiple effects, such as RGS14, is that it elicit these unusual protective effects mediated by several distal signaling pathways, which in their combination are likely more salutary than any one of the individual mechanisms.

描述（由适用提供）：G蛋白信号14（RGS14）在心脏中的调节剂的作用从未被研究过，我们发现RGS14 KO小鼠免受急性和慢性缺血的不良影响，通过血管生成/动脉生成的不良影响，可以通过血管生成/动脉生成，可以通过肌动质量的重塑和发育。为了实现该提议的目的，我们将研究以下假设：我们的第一个假设是RGS14的破坏是一种通过血管生成和动脉生成来保护心脏免受慢性心肌缺血的新机制。我们的第二个假设是，急性和慢性缺血性保护的机制涉及MEK/ERK途径的GI AC/CAMP和RAS介导的激活，因此一氧化氮（NO）/VEGF激活以及阻断氧化物应激。 RGS14敲除（KO）小鼠特别新颖的特征是它可以防止急性和慢性心肌缺血并诱导动脉生成/血管生成的能力。第二种新颖的特征是研究抑制具有多种作用的基因的重要性，例如RGS14，它引起了通过几种不同的信号传导途径介导的这些异常的保护作用，它们的结合可能比任何一种单个机制都更有益来自。