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Effects of a Proteasome Inhibitor on Cardiomyocytes in a Pressure-Overload Hypertrophy Rat Model: An Animal Study
The Korean Journal of Thoracic and Cardiovascular Surgery ; : 144-152, 2017.
Article Dans Anglais | WPRIM | ID: wpr-111254
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.
Sujets)

Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Cardiomyopathie hypertrophique / Fibrose / Lymphocytes B / Ubiquitines / Récepteurs aux androgènes / Facteur de transcription NF-kappa B / Hypertrophie ventriculaire gauche / Constriction / Modèles animaux / Myocytes cardiaques Type d'étude: Étude pronostique Limites du sujet: Animaux langue: Anglais Texte intégral: The Korean Journal of Thoracic and Cardiovascular Surgery Année: 2017 Type: Article

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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Cardiomyopathie hypertrophique / Fibrose / Lymphocytes B / Ubiquitines / Récepteurs aux androgènes / Facteur de transcription NF-kappa B / Hypertrophie ventriculaire gauche / Constriction / Modèles animaux / Myocytes cardiaques Type d'étude: Étude pronostique Limites du sujet: Animaux langue: Anglais Texte intégral: The Korean Journal of Thoracic and Cardiovascular Surgery Année: 2017 Type: Article