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Role of Oxytocin and C-Myc Pathway in Cardiac Remodeling in Neonatal Rats Undergoing Cardiac Apical Resection Publisher Pubmed



Khori V1 ; Mohammad Zadeh F1 ; Tavakolifar B2 ; Alizadeh AM3, 4 ; Khalighfard S4, 5 ; Ghandian Zanjan M1 ; Gharghi M1 ; Khodayari S5, 6 ; Khodayari H5, 6 ; Keshavarz P7
Authors
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Authors Affiliations
  1. 1. Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
  2. 2. Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran
  3. 3. Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Breast Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. International Center for Personalized Medicine, Dusseldorf, Germany
  7. 7. Department of Radiology, Tbilisi State Medical University (TSMU), Tbilisi, Georgia

Source: European Journal of Pharmacology Published:2021


Abstract

Oxytocin (OT) is a nonapeptide hormone that can improve cardiomyocyte proliferation, suggesting a potential heart regeneration function. Here, we investigated the role of oxytocin and the c-Myc pathway in cardiac remodeling in neonatal rats undergoing cardiac apical resection. We have utilized a knockout of oxytocin receptor (OTR) with OTR-shRNA. A neonatal rat model of cardiac resection (≈10%–15%) was first established. The protein levels of OTR and c-Myc and the expression of cyclin d1 and c-Myc genes were then evaluated in the cardiac tissues at 1, 7, and 21 days after cardiac resection. We also analyzed the proliferation of cardiomyocytes through α-actinin, BrdU, and ki-67 markers. At last, the hemodynamic and electrophysiologic functions were evaluated eight weeks after cardiac resection. At 21 days, the regeneration of cardiomyocytes was repaired among rats in the control and resection groups, while OTR-shRNA groups were failed to improve. Inhibition of OTR failed cardiac regeneration and reduced the number of proliferating cardiomyocytes. The c-Myc protein was significantly reduced in the OTR-shRNA injection hearts. Moreover, we have severely found a depressed heart function in the OTR-shRNA injection animals. These observations revealed that the OT must improve cardiac remodeling in neonatal rat hearts by regulating the c-Myc pathway. © 2021 Elsevier B.V.