The role of hippo signaling pathway in physiological cardiac hypertrophy

Gholipour, M ; Sharif University of Technology | 2020

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  1. Type of Document: Article
  2. DOI: 10.34172/bi.2020.32
  3. Publisher: Tabriz University of Medical Sciences , 2020
  4. Abstract:
  5. Introduction: The role of Hippo signaling pathway, which was identified by genetic studies as a key regulator for tissue growth and organ size, in promoting physiological cardiac hypertrophy has not been investigated. Methods: Fourteen male Wistar rats were randomly assigned to the exercise and control groups. The exercise group ran 1 hour per day, 5 days/week, at about 65%-75% VO2max on the motor-driven treadmill with 15ºslope, and the control group ran 15 min/d, 2 days/ week at 9 m/min (0ºinclination), throughout the eight-week experimental period. Forty-eight hours after the last session, hearts were dissected and left ventricles were weighed and stored for subsequent RT-PCR analysis. Results: Despite a significant increase in the MAP4k1 expression levels in the exercise group (P= 0.001), the Mst1 expression was inhibited compared to the control group (P< 0.001) which was followed by suppression of Lats1 expression (P= 0.001). Compared with the control group, significant increases were observed in heart weight/body weight (P= 0.024) and left ventricular weight/body weight (P= 0.034) ratios in the exercise group. The H&E staining confirmed the cardiac hypertrophy that may be partly due to a significant increase in Yap1 expression level compared with the control group (P< 0.001), which was confirmed by Western blot analysis. Conclusion: Increased MAP4K1 expression did not influence Lats1 activation. The exercise training protocol suppressed Mst1 and Lats1 (Hippo pathway) and caused an increase in Yap1 expression level, which led to physiological cardiac hypertrophy in healthy rats. Further studies are suggested to apply this exercise protocol for the prevention and/or rehabilitation of cardiovascular disease and health promotion. © 2020 The Author(s). This work is published by BioImpacts as an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/). Non-commercial uses of the work are permitted, provided the original work is properly cited
  6. Keywords:
  7. Cardiomyocyte adaptation ; Left ventricular hypertrophy ; Molecular signaling ; Uphill-treadmill running ; Wistar rat ; Lats1 protein ; Mst1 protein ; Protein ; Transcription factor Yap1 ; Unclassified drug ; Animal experiment ; Animal model ; Article ; Body weight ; Controlled study ; Endurance training ; Exercise intensity ; Gene expression ; Heart left ventricle ; Heart left ventricle hypertrophy ; Heart ventricle hypertrophy ; Heart weight ; Hippo signaling ; Male ; Nonhuman ; Protein expression ; Rat ; Real time polymerase chain reaction ; Transcription initiation ; Western blotting
  8. Source: BioImpacts ; Volume 10, Issue 4 , 2020 , Pages 251-257
  9. URL: https://bi.tbzmed.ac.ir/Article/bi-21802