Korean J Thorac Cardiovasc Surg.  2017 Jun;50(3):144-152. 10.5090/kjtcs.2017.50.3.144.

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

• Kim IS
• Jo WM

• KMID: 2381896
• DOI: http://doi.org/10.5090/kjtcs.2017.50.3.144

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.

Keyword

Cardiomyopathy, hypertrophic; Ubiquitins; Proteasome inhibitors; MG132; Receptors, androgen; NF-kappa B

MeSH Terms

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
NF-kappa B
Proteasome Endopeptidase Complex
Proteasome Inhibitors
Receptors, Androgen
Ubiquitins