(-)-Epicatechin Suppresses Angiotensin II-induced Cardiac Hypertrophy via the Activation of the SP1/SIRT1 Signaling Pathway

Cell Physiol Biochem. 2017;41(5):2004-2015. doi: 10.1159/000475396. Epub 2017 Apr 13.

Abstract

Background/aims: Flavonol (-)-epicatechin (EPI) is present in high amounts in cocoa and tea products, and has been shown to exert beneficial effects on the cardiovascular system. However, the precise mechanism of EPI on cardiomyocyte hypertrophy has not yet been determined. In this study, we examined whether EPI could inhibit cardiac hypertrophy.

Methods: We utilised cultured neonatal mouse cardiomyocytes and mice for immunofluorescence, immunochemistry, qRT-PCR, and western blot analyses.

Results: 1µM EPI significantly inhibited 1µM angiotensin II (Ang II)-induced increase of cardiomyocyte size, as well as the mRNA and protein levels of ANP, BNP and β-MHC in vitro. The effects of EPI were accompanied with an up-regulation of SP1 and SIRT1, and were abolished by SP1 inhibition. Up-regulation of SP1 could block Ang II-induced increase in cardiomyocyte size, as well as the mRNA and protein levels of ANP, BNP and β-MHC, and increase the protein levels of SIRT1 in vitro. Moreover, 1 mg/kg body weight/day EPI significantly inhibited mouse cardiac hypertrophy induced by Ang II, which could be eliminated by SP1 inhibition in vivo.

Conclusion: Our data indicated that EPI inhibited AngII-induced cardiac hypertrophy by activating the SP1/SIRT1 signaling pathway.

Keywords: Angiotensin II; Cardiac hypertrophy; Epicatechin; SIRT1; SP1.

MeSH terms

  • Angiotensin II / adverse effects*
  • Angiotensin II / pharmacology
  • Animals
  • Cardiomegaly* / chemically induced
  • Cardiomegaly* / drug therapy
  • Cardiomegaly* / metabolism
  • Cardiomegaly* / pathology
  • Catechin / pharmacology*
  • Mice
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Signal Transduction / drug effects*
  • Sirtuin 1 / metabolism*
  • Sp1 Transcription Factor / metabolism*

Substances

  • Sp1 Transcription Factor
  • Angiotensin II
  • Catechin
  • Sirt1 protein, mouse
  • Sirtuin 1