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.
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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