Basic Progress and Future Therapeutic Perspectives of Relaxin in Ischemic Heart Disease
Abstract: Relaxin has been validated as a cardiotropic hormone, being produced by the heart and acting on specific heart receptors. Evidence is accumulating that it could hamper the pathophysiologic mechanisms of ischemic heart disease. Time is ripe to study relaxin as a cardiotropic drug, as recombinant human relaxin (hrRLX) is now available and previous clinical trials have shown a virtual lack of toxicity and adverse side effects, even at high doses. Our recent observations suggest that relaxin, besides being a preventative agent, may also be effective in the treatment of acute myocardial infarction and may be an adjuvant for precursor cell grafting to repair postinfarct myocardium. In a swine model of myocardial infarction currently used to test cardiotropic drugs due to its similarities with human ischemic heart disease, hrRLX, given at reperfusion upon 30 min of ischemia, markedly reduced serum and tissue markers of myocardial injury, cardiomyocyte apoptosis and leukocyte recruitment, resulting in overall improvement in cardiac performance compared with the controls. In in vitro mixed cultures of mouse skeletal myoblasts and adult rat cardiomyocytes, relaxin increased gap junction formation and potentiated gap junction-mediated intercellular exchanges and signaling between the coupled cells. In view of the therapeutic use of myoblast grafting for cardiac repair, relaxin could hence favor the electromechanical coupling of grafted myoblasts with the resident cardiomyocytes and facilitate their transdifferentiation towards a cardiac phenotype. Relaxin, therefore, shows promising therapeutic potential in cardiology and cardiac surgery.
heart myocardial infarction cell cardiomyoplasty