Cardioprotective Effect of Growth Hormone Releasing Hormone

生长激素释放激素的心脏保护作用

• 批准号: 8411600
• 负责人: Joshua M Hare
• 金额: $ 64.93万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8411600
• 关键词: 1-Phosphatidylinositol 3-Kinase; Acute; Acute myocardial infarction; Advanced Development; Adverse effects; Aftercare; Agonist; Animal Model; Animals; Apoptosis; Apoptotic; Area; Awareness; Biological Assay; Blood Vessels; Cardiac; Cardiac Myocytes; Cell Survival; Cells; Chronic; Cicatrix; Coupling; Data; Development; Evaluation; Failure; Family suidae; Functional disorder; Genes; Goals; Grant; Growth; Growth Factor; Healed; Heart; Histologic; Hormones; Hypertrophy; Hypothalamic Hormones; In Vitro; Infarction; Injection of therapeutic agent; Injury; Insulin-Like Growth Factor I; Ischemia; Laboratories; Left Ventricular Remodeling; Magnetic Resonance Imaging; Mediating; Modeling; Molecular; Muscle Cells; Myocardial; Myocardial Infarction; Myocardium; Natural regeneration; Pathway interactions; Performance; Prevention; Process; Proto-Oncogene Protein c-kit; Publishing; Rattus; Receptor Activation; Receptor Mediated Signal Transduction; Recovery of Function; Regulation; Reperfusion Therapy; Rodent; Role; Signal Pathway; Signal Transduction; Somatotropin; Somatotropin-Releasing Hormone; Specificity; Stem cells; Structure; Testing; Therapeutic; Ventricular; Ventricular Remodeling; Work; cardiac repair; cytokine; growth hormone-releasing hormone receptor; healing; hemodynamics; improved; in vivo; insight; interest; migration; molecular marker; novel; novel therapeutics; preconditioning; programs; protective effect; receptor; regenerative; research study; response; self-renewal; stem cell therapy; translational study; treatment strategy

There is growing awareness that the heart has receptors for a wide range of cytokines and growth factors, activation of which can enhance myocyte survival and growth. While there has been interest in the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis in the regulation of cardiac development and performance, only recently is it appreciated that the hypothalamic hormone, GH releasing hormone also exerts cardiac signaling activity, and that the GHRH receptor is present on myocytes. Recently, we demonstrated that a potent growth hormone releasing hormone agonist (GHRH-A: JI-38) stimulated substantial cardiac repair following acute ischemic injury without stimulating unwanted side effects associated with the GH axis. In addition, Granata et al. demonstrated that GHRH(1-44) promotes survival of cardiomyocytes following ischemia reperfusion. The availability of potent GHRH agonists offers a major new therapeutic opportunity. The overall goal of this project is to use well-validated animal models of ischemic injury and LV dysfunction (rodent and porcine, in use in our laboratory) to test the hypothesis that activation of cardiac GHRH receptors by potent agonists can reverse remodeling and improve recovery of functional performance following myocardial infarction (MI). We propose a program of work to determine the mechanism of action and manifestations of this effect. We will in three aims test the following hypothesis: To test the hypothesis that the effects of GHRH-A are mediated by direct receptor activation of the GHRH-R within the heart; To test the hypothesis that GHRH-A directly activates endogenous cardiac stem cells; Investigate the protective effects of GHRH agonist in a pig model of MI. This proposal has major implications for developing a promising new treatment strategy for the prevention and reversal of remodeling following MI.

越来越多的人意识到心脏有多种细胞因子的受体