Heart failure (HF) is defined as occurring when the heart is unable to provide adequate blood flow and oxygen to organs across the body. Currently, a diagnosis of HF is made using a combination of clinical features, cardiac imaging, and detection of certain biomarkers in the circulation, notably BNP. However, a biomarker specific to cardiac tissue and that reflects the heart’s contractile state is lacking. Our group is characterizing the growth hormone secretagogue receptor (GHSR) and its ligand ghrelin as possible cardiac-specific biomarkers for HF. We have previously developed a fluorescent analog of ghrelin, Ghrelin(1-18, Lys18(Cy5), to detect GHSR in cardiac tissue in situ. We hypothesize that GHSR and ghrelin are biomarkers for the early detection of HF. We obtained samples of cardiac tissue from 10 cardiac transplant patients at the time of organ harvesting and serial post-transplant biopsies. Samples from the LV and RA of the explanted hearts, and biopsies from the newly-transplanted hearts (weekly for 4 weeks, monthly for 6 months, and 1 year post-Tx). GHSR levels were measured using Ghrelin(1-18, Lys18(Cy5) and ghrelin and BNP were measured using fluorescent antibodies. All samples were quantified using fluorescence microscopy. Fibrotic tissue was detected using Masson’s trichrome stain. Levels of all markers were compared between the explanted heart and the healthy biopsies using two-tailed t-test, one-way ANOVA and Tukey’s test and Pearson’s correlation (p < 0.05). GHSR and fibrosis levels increased and were highly variable in explanted hearts when compared to the healthy biopsies which had a much lower level of variability. Within 3 individual patients, there were significant differences (p < 0.001, p < 0.05, p < 0.01 respectively) between the explanted heart (LV and RA) and the short-term biopsies of the healthy heart (weeks 1-4) of both GHSR and ghrelin but not BNP. Within the entire transplant patient cohort (n=10), there was a strong positive correlation between both ghrelin and BNP (r2=0.575, p < 0.0001) and ghrelin and GHSR (r2=0.7033, p < 0.0001). GHSR and ghrelin showed elevated expression and significant differences in 3 of the 10 patients with end stage HF where BNP showed no significant differences indicating the increased sensitivity of GHSR and ghrelin in HF detection. Correlation between ghrelin and BNP, and ghrelin and GHSR in cardiac tissue may show evidence of a ghrelin/GHSR system working independently in the myocardium. These results indicate the potential use of ghrelin and GHSR as new cardiac-specific biomarkers that can help with the detection of HF.View Large Image Figure ViewerDownload Hi-res image Download (PPT)