Atorvastatin prevents Angiotensin II induced myocardial hypertrophy in vitro via CCAAT/enhancer-binding protein β

Biochem Biophys Res Commun. 2017 Apr 29;486(2):423-430. doi: 10.1016/j.bbrc.2017.03.057. Epub 2017 Mar 15.

Abstract

Previous evidences suggested that atorvastatin not only reduced blood lipids but also reduced myocardial hypertrophy and remodeling. And it was reported that C/EBPβ (CCAAT/enhancer-binding protein β) played a pivotal role both in the physiologic and pathological cardiac hypertrophy. However, it has not been reported before whether this signaling pathway of C/EBPβ participates in protective effect of atorvastatin for hypertrophy cardiomyocytes. In present study, We found that overexpression of C/EBPβ significantly abrogated the effect of atorvastatin on increasing Bcl-2/Bax and PGC-1α while the early and late apoptosis rate increased and mitochondrial membrane potential (MMP) was reduced. In conclusion, we further identified the protective effect of atorvastatin on hypertrophic cardiomyocytes induced by Angiotensin II by rescuing the MMP and inhibiting apoptosis, which might be at least partly attributed to down-regulation of C/EBPβ. And C/EBPβ might be a new target to rescue mitochondrion function and apoptosis in pathological cardiac hypertrophy.

Keywords: Apoptosis; Atorvastatin; C/EBPβ; Myocardial hypertrophy; PGC-1α.

MeSH terms

  • Angiotensin II / pharmacology*
  • Angiotensin Receptor Antagonists / pharmacology*
  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Atorvastatin / pharmacology*
  • CCAAT-Enhancer-Binding Protein-beta / genetics*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cell Line
  • Gene Expression Regulation
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Signal Transduction
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Angiotensin Receptor Antagonists
  • Anticholesteremic Agents
  • Bax protein, rat
  • Bcl2 protein, rat
  • CCAAT-Enhancer-Binding Protein-beta
  • Cebpb protein, rat
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Angiotensin II
  • Atorvastatin