Key result
MG132 administration significantly reduced androgen receptor protein expression compared to control (0.308 vs 0.531, p=0.013) in a rat model of pressure-overload hypertrophic cardiomyopathy.
Why the study?
Does MG132 improve pathophysiologic outcomes and alter AR and NF-κB expression in a pressure-overload hypertrophy rat model?
Does MG132 improve pathophysiologic outcomes and alter AR and NF-κB expression in a pressure-overload hypertrophy rat model?
Answers are grounded in this paper and cite their sources.
MG132 suppresses androgen receptor expression and reduces fibrosis in a pressure-overload ventricular hypertrophy rat model, suggesting a potential cardioprotective mechanism via the ubiquitin-proteasome system.
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.
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Kim et al. (2017) studied Left ventricular hypertrophy (n=30). MG132 vs. Control (no MG132) was evaluated on Androgen receptor (AR) protein expression (p=0.013). MG132 administration significantly reduced androgen receptor protein expression compared to control (0.308 vs 0.531, p=0.013) in a rat model of pressure-overload hypertrophic cardiomyopathy.
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