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Changes in the cardiac GHSR1a-ghrelin system correlate with myocardial dysfunction in diabetic cardiomyopathy in mice
Journal of the Endocrine Society
  • Rebecca Sullivan, Lawson Health Research Institute
  • Rebecca McGirr, Lawson Health Research Institute
  • Shirley Hu, Western University
  • Alice Tan, Western University
  • Derek Wu, Western University
  • Carlie Charron, Western University
  • Tyler Lalonde, Western University
  • Edith Arany, Western University
  • Subrata Chakrabarti, Western University
  • Leonard Luyt, Western University
  • Savita Dhanvantari, Lawson Health Research Institute
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Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are present in cardiac tissue. Activation of GHSR1a by ghrelin promotes cardiomyocyte contractility and survival, and changes in myocardial GHSR1a and circulating ghrelin track with end-stage heart failure, leading to the hypothesis that GHSR1a is a biomarker for heart failure. We hypothesized that GHSR1a could also be a biomarker for diabetic cardiomyopathy (DCM). We used two models of streptozotocin (STZ)-induced DCM: group 1, adult mice treated with 35 mg/kg STZ for 3 days; and group 2, neonatal mice treated with 70 mg/kg STZ at days 2 and 5 after birth. In group 1, mild fasting hyperglycemia (11 mM) was first detected 8 weeks after the last injection, and in group 2, severe fasting hyperglycemia (20 mM) was first detected 1 to 3 weeks after the last injection. In group 1, left ventricular function was slightly impaired as measured by echocardiography, and Western blot analysis showed a significant decrease in myocardial GHSR1a. In group 2, GHSR1a levels were also decreased as assessed by Cy5-ghrelin(1-19) fluorescence microscopy, and there was a significant negative correlation between GHSR1a levels and glucose tolerance. There were significant positive correlations between GHSR1a and ghrelin and between GHSR1a and sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), a marker for contractility, but not between GHSR1a and B-type natriuretic peptide, a marker for heart failure. We conclude that the subclinical stage of DCM is accompanied by alterations in the myocardial ghrelin-GHSR1a system, suggesting the possibility of a biomarker for DCM.

Citation Information
Rebecca Sullivan, Rebecca McGirr, Shirley Hu, Alice Tan, et al.. "Changes in the cardiac GHSR1a-ghrelin system correlate with myocardial dysfunction in diabetic cardiomyopathy in mice" Journal of the Endocrine Society Vol. 2 Iss. 2 (2018) p. 178 - 189
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