Anti-apoptotic, anti-fibrotic, and positive inotropic effects of ghrelin and GHRP on rat and mouse cardiac myocytes [ 2007 - 2009 ]

Research Grant

Researchers: Prof Chen Chen (Principal investigator) ,  Dr Morag Young

Brief description Growth hormone (GH) is a protein hormone secreted from an endocrine organ, the pituitary gland, below the brain. Synthetic GH-releasing peptides (GHRPs) and endogenous GHRP (ghrelin) possess many other physiological functions in addition to the release of GH. GHRPs have been shown to affect cardiac function in animals and humans through their specific receptors. We recently demonstrated at single cell level that GHRPs increased contraction of cardiac muscle cells and protected them from the programmed cell death which occurs in heart failure and myocardial infarction. We also demonstrated that GHRPs protected the heart in chronic heart failure and alleviated functional loss of the heart in experimental heart failure models. Preliminary results now indicate that GHRPs prevent cardiac fibrosis, which accounts for cardiac dysfunction after heart failure and infarction. It is proposed in this project to clarify the mechanism underlying the action of GHRPs in (1) cardiac functional enhancing; (2) anti-cell death; (3) anti-fibrosis effects, in primary cultured rat myocytes in vitro and in cardiac diseased mouse models in vivo. By completing this project, we will be able to (1) better understand the physiological role of ghrelin in the regulation of cardiac function; and (2) clarify the potential for therapeutic use of GHRPs in the treatment of chronic heart failure, a disease affecting 1-2% of the population of Australia, with 5 year mortality rates about 65%.

Funding Amount $AUD 442,530.75

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant