Effects of a Proteasome Inhibitor on Cardiomyocytes in a Pressure-Overload Hypertrophy Rat Model: An Animal Study

• Published in: The Korean journal of thoracic and cardiovascular surgery Vol. 50; no. 3; pp. 144 - 152
• Main Authors: Kim, In-Sub, Jo, Won-Min
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society for Thoracic and Cardiovascular Surgery 01.06.2017; Korean Society for Thoracic and Cardiovascular Surgery
• Subjects: androgen; Basic Research; Cardiomyopathy; hypertrophic; MG132; NF-kappa B; Proteasome inhibitors; Receptors; Ubiquitins; MG132; NF-kappa B; Cardiomyopathy, hypertrophic; Ubiquitins; Proteasome inhibitors; Receptors, androgen
• ISSN: 2233-601X; 2093-6516
• DOI: 10.5090/kjtcs.2017.50.3.144

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. 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. 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). 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.