Dynamics of the ghrelin/growth hormone secretagogue receptor system in the human heart before and after cardiac transplantation

Currently, the early preclinical detection of left ventricular dysfunction is difficult because biomarkers are not specific for the cardiomyopathic process. The underlyingmolecular mechanisms leading to heart failure remain elusive, highlighting the need for identification of cardiac-specific markers. The growth hormone secretagogue receptor (GHSR) and its ligand ghrelin are present in cardiac tissue and are known to contribute to myocardial energetics. Here, we examined tissue ghrelin-GHSR levels as specific markers of cardiac dysfunction in patients who underwent cardiac transplantation. Samples of cardiac tissue were obtained from 10 patients undergoing cardiac transplant at the time of organ harvesting and during serial posttransplant biopsies.Quantitative fluorescencemicroscopy using a fluorescent ghrelin analog was used to measure levels of GHSR, and immunofluorescence was used tomeasure levels of ghrelin, B-type natriuretic peptide (BNP), and tissuemarkers of cardiomyocyte contractility and growth. GHSR and ghrelin expression levels were highly variable in the explanted heart, less in the grafted heart biopsies.GHSR and ghrelinwere strongly positively correlated, and both markers were negatively correlated with left ventricular ejection fraction. Ghrelin had stronger positive correlations than BNP with the signaling markers for contractility and growth. These data suggest that GHSR-ghrelin have potential use as an integrated marker of cardiac dysfunction. Interestingly, tissue ghrelin appeared to be a more sensitive indicator than BNP to the biochemical processes that are characteristic of heart failure. This work allows for further use of ghrelin-GHSR to interrogate cardiac-specific biochemical mechanisms in preclinical stages of heart failure (HF).