Effects of a proteasome inhibitor on cardiomyocytes in a pressure-overload hypertrophy rat model: An animal study

In Sub Kim, Won Min Jo

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of NF-κB and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model. Methods: We constructed a transverse aortic constriction (TAC)-induced LVH rat model with 3 groups: sham (TAC-sham, n=10), control (TAC-cont, n=10), and MG132 administration (TAC-MG132, n=10). MG-132 (0.1 mg/kg) was injected for 4 weeks in the TAC-MG132 group. Pathophysiologic evaluations were performed and the expression of AR and NF-κB was measured in the left ventricle. Results: Fibrosis was prevalent in the pathologic examination of the TAC-cont model, and it was reduced in the TAC-MG132 group, although not significantly. Less expression of AR, but not NF-κB, was found in the TAC-MG132 group than in the TAC-cont group (p<0.05). Conclusion: MG-132 was found to suppress AR in the TAC-CMP model by blocking the UPS, which reduced fibrosis. However, NF-κB expression levels were not related to UPS function.

Original languageEnglish
Pages (from-to)144-152
Number of pages9
JournalKorean Journal of Thoracic and Cardiovascular Surgery
Volume50
Issue number3
DOIs
Publication statusPublished - 2017

Keywords

  • Androgen
  • Cardiomyopathy
  • Hypertrophic
  • MG132
  • NF-kappa B
  • Proteasome inhibitors
  • Receptors
  • Ubiquitins

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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