Effects of melanocortin receptor modulation on hypertrophic responses in cardiomyocytes

Abstract

After cardiac stress such as that occurring during myocardial infarction the heart undergoes pathological remodelling consisting of cardiomyocyte hypertrophy, interstitial fibrosis, contractile dysfunction, cell death and ventricular dilatation. It is due to this remodelling that the survivability is 10% at 10 years post-infarction. In this study we explored the possible cardioprotective effects of melanocortin receptor activation in an initial search for a treatment for cardiac remodelling. ELISA tests were used to study the signalling cascade of melanocortin receptor activation and qPCRs were used to study gene expression changes. Using an established rat cardiomyocyte cell line and primary mouse cardiomyocytes it was established that activation of all melanocortin receptors results in a cardioprotective response through the downregulation of pro-hypertrophic genes. We were also able to determine through independent activation of the receptors for melanocortins that the receptors for melanocortin 1 and 5 were the ones responsible for the cardioprotective response, with melanocortin receptor 5 activation providing the strongest cardioprotective effect. Further study of these receptors and their cardioprotective effects could lead to a treatment for cardiac hypertrophy.