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

Rebecca Sullivan, Varinder K Randhawa, Tyler Lalonde, Tina Yu, Bob Kiaii, Leonard Luyt, Gerald Wisenberg, Savita Dhanvantari
doi: https://doi.org/10.1101/2020.07.13.201319
Rebecca Sullivan
1Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
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  • For correspondence: rsulli4@uwo.ca
Varinder K Randhawa
5Cardiology Division, Toronto General Hospital, University Health Network, and University of Toronto, Ontario, Canada
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Tyler Lalonde
2Chemistry, Western University, London, Ontario, Canada
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Tina Yu
6Medical Biophysics, Western University, London, Ontario, Canada
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Bob Kiaii
8Cardiac Surgery, Western University, London, Ontario, Canada
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Leonard Luyt
2Chemistry, Western University, London, Ontario, Canada
4Oncology, London Regional Cancer Program, Western University, London, Ontario, Canada
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Gerald Wisenberg
3Imaging Program, Lawson Health Research Institute, London, Ontario, Canada
6Medical Biophysics, Western University, London, Ontario, Canada
7Cardiac Imaging Research, Lawson Health Research Institute, London, Ontario, Canada
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Savita Dhanvantari
1Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
3Imaging Program, Lawson Health Research Institute, London, Ontario, Canada
6Medical Biophysics, Western University, London, Ontario, Canada
9Metabolism and Diabetes, Lawson Health Research Institute, London, Ontario, Canada
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Abstract

The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR are altered significantly in late stages of heart failure and cardiomyopathy, when left ventricular (LV) function is failing. We examined the relationship of GHSR with ghrelin in cardiac tissue from patients with valvular disease with no detectable changes in LV function. Biopsy samples from the LV and left atrium (LA) were obtained from 25 patients with valvular disease (of whom 13 also had coronary artery disease) and preserved LV ejection fraction, and compared control samples obtained via autopsy. Using quantitative confocal fluorescence microscopy, levels of GHSR were determined using a fluorescent peptide analog of ghrelin, Cy5-ghrelin(1-19); 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 only diseased tissue. Ghrelin and BNP significantly correlated in the LV and strongly co-localized to the same intracellular compartment in both diseased and control tissue. GHSR, ghrelin and BNP all strongly and significantly correlated with SERCA2a in the LV of diseased tissue only. Our results suggest that the dynamics of the myocardial ghrelin/GHSR axis is altered in cardiovascular disease in the absence of measurable changes in heart function, and may accompany a regional shift in endocrine programming.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 05, 2020.
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Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease
Rebecca Sullivan, Varinder K Randhawa, Tyler Lalonde, Tina Yu, Bob Kiaii, Leonard Luyt, Gerald Wisenberg, Savita Dhanvantari
bioRxiv 2020.07.13.201319; doi: https://doi.org/10.1101/2020.07.13.201319
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Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease
Rebecca Sullivan, Varinder K Randhawa, Tyler Lalonde, Tina Yu, Bob Kiaii, Leonard Luyt, Gerald Wisenberg, Savita Dhanvantari
bioRxiv 2020.07.13.201319; doi: https://doi.org/10.1101/2020.07.13.201319

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