Ghrelin suppresses cardiac fibrosis of post-myocardial infarction heart failure rats by adjusting the activin A-follistatin imbalance

Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease

“…In the same study, no differences in GHSR density were observed in the RA or the LV between the ischemic heart disease or dilated cardiomyopathy to the control tissues 30 . Our findings also showed no changes in myocardial GHSR as measured by Cy5-ghrelin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), and a relatively weak correlation with ghrelin, suggesting that more dramatic changes in GHSR may occur at the site of vascular tissue injury or dysfunction.…”

“…Biopsy samples from the left ventricle (LV) and right atrium (RA) were obtained from 25 patients with valvular disease (of whom 13 also had coronary artery disease) and preserved left ventricular ejection fraction, and compared to control samples that were obtained via autopsy. Using quantitative confocal fluorescence microscopy, levels of GHSR were determined using a fluorescent peptide analog of ghrelin, Cy5-ghrelin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19); ghrelin, the heart failure marker natriuretic peptide type-b (BNP), and contractility marker sarcoplasmic reticulum ATPase pump (SERCA2a) were measured by immunofluorescence. A positive correlation between GHSR and ghrelin was apparent in diseased tissue, but not in control tissue.…”

“…Apoptosis is decreased upon GHSR activation through extracellular signal-related kinases 1/2 (ERK1/2) and AKT serine kinases 5,6 and inhibition of caspase-3 and 9 7 . Fibrosis deposition through collagen I and III production is also minimized in the heart after ghrelin administration 8,9 . Therefore, the ghrelin/GHSR axis within the myocardium plays a critical role in the maintenance of cardiomyocyte function and survival.…”

“…Graphs indicate quantification of integrated densities using linear regression between Cy5-ghrelin(1-19) and ghrelin (r = 0.3995; p=0.0318) in the entire patient cohort where each dot represents one patient sample (B). Regional analysis showed a significant linear regression of Cy5-ghrelin(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and ghrelin in the RA (r = 0.4859; p=0.0299) but not the LV (p=ns) (C). In control tissue, there was no correlation between Cy5-ghrelin(1-19) and ghrelin (p=ns) (D).…”

“…Cy5-ghrelin(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) was added to tissue sections for 30 min. Sections were washed twice with PBS, incubated 8 min with DAPI nuclear stain (1:1000), and mounted with ProLong Diamond antifade (Life Technologies) to prevent the tissues from photobleaching.For control cardiac tissue, all sections were deparaffinized with increasing concentrations of alcohol solutions (70%-90%).…”