Effects of a Proteasome Inhibitor on Cardiomyocytes in a Pressure-Overload Hypertrophy Rat Model: An Animal Study.
10.5090/kjtcs.2017.50.3.144
- Author:
In Sub KIM
1
;
Won Min JO
Author Information
1. Department of Thoracic and Cardiovascular Surgery, Korea University College of Medicine, Korea.
- Publication Type:Original Article
- Keywords:
Cardiomyopathy, hypertrophic;
Ubiquitins;
Proteasome inhibitors;
MG132;
Receptors, androgen;
NF-kappa B
- MeSH:
Animals;
Animals*;
B-Lymphocytes;
Cardiomyopathy, Hypertrophic;
Constriction;
Fibrosis;
Heart Failure;
Heart Ventricles;
Hypertrophy*;
Hypertrophy, Left Ventricular;
Models, Animal*;
Myocytes, Cardiac*;
NF-kappa B;
Proteasome Endopeptidase Complex*;
Proteasome Inhibitors*;
Proteolysis;
Rats*;
Receptors, Androgen;
Ubiquitins
- From:The Korean Journal of Thoracic and Cardiovascular Surgery
2017;50(3):144-152
- CountryRepublic of Korea
- Language:English
-
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.
