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Molecular and Cellular Biochemistry

, Volume 450, Issue 1–2, pp 25–34 | Cite as

Ivabradine improved left ventricular function and pressure overload-induced cardiomyocyte apoptosis in a transverse aortic constriction mouse model

  • Yihui Yu
  • Zuoying Hu
  • Bing Li
  • Zhimei Wang
  • Shaoliang ChenEmail author
Article
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Abstract

This study aimed to investigate the effects and molecular mechanisms of ivabradine in preventing cardiac hypertrophy in an established transverse aortic constriction (TAC) mouse model. A total of 56 male C57BL/6 mice were randomly assigned into the following seven groups (8 mice per group): sham, TAC model, Iva-10 (10 mg/kg/day ivabradine), Iva-20 (20 mg/kg/day ivabradine), Iva-40 (40 mg/kg/day ivabradine), Iva-80 (80 mg/kg/day ivabradine), and Rap (rapamycin, a positive control). Echocardiography and left ventricular hemodynamics were performed. Hematoxylin-eosin (H&E), Masson’s trichome staining, and TUNEL assays were conducted to evaluate cardiac hypertrophy, fibrosis, and apoptosis, respectively. Western blotting was performed to detect the expression of proteins related to the PI3K/Akt/mTOR/p70S6K pathway. Ivabradine could effectively improve left ventricular dysfunction and hypertrophy induced by TAC in a dose-independent manner. Moreover, no obvious change in heart rate (HR) was observed in the TAC and Rap groups, whereas a significant decrease in HR was found after ivabradine treatment (P < 0.05). Cardiac hypertrophy, fibrosis, and apoptosis induced by TAC were notably suppressed after either rapamycin or ivabradine treatment (P < 0.05). Ivabradine and rapamycin also decreased the expression of PI3K/Akt and mTOR induced by TAC. Ivabradine improved cardiac hypertrophy and fibrosis as well as reduced cardiomyocyte apoptosis via the PI3K/Akt/mTOR/p70S6K pathway in TAC model mice.

Keywords

Ivabradine Transverse aortic constriction Cardiac hypertrophy Apoptosis PI3K/Akt/mTOR pathway 
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Notes

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interests to state.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yihui Yu
    • 1
  • Zuoying Hu
    • 1
  • Bing Li
    • 1
  • Zhimei Wang
    • 1
  • Shaoliang Chen
    • 1
    Email author
  1. 1.Division of Cardiovascular Medicine, Department of Medicine, Nanjing First HospitalNanjing Medical UniversityNanjingChina

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