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. 2013 Nov;1(6):935-939.
doi: 10.3892/br.2013.165. Epub 2013 Sep 12.

Inhibition of ubiquitin protein expression and 20S proteasome activity by irbesartan prevents post-infarction ventricular remodeling and decreases TNF-α generation

Naiju Zhang  1 , Tianping Chen  2 , Chunfang Liu  2 , Bi Tang  2 , Ling Nie  3 , Huiling An  3 , Duilan Zhao  3 , Li Pan  3 , Meiling Yu  1
Affiliations

Inhibition of ubiquitin protein expression and 20S proteasome activity by irbesartan prevents post-infarction ventricular remodeling and decreases TNF-α generation

Naiju Zhang et al. Biomed Rep. 2013 Nov.

Abstract

Myocardial infarction (MI) may induce severe alterations of the cardiac contractile function that may, in turn, lead to heart failure (HF). The ubiquitin-proteasome system (UPS) plays a critical role in cardiac remodeling following MI. Angiotensin II type 1 receptor (AT1R) blockers effectively prevent left ventricular (LV) remodeling. However, it has not been elucidated whether the preventive effect of AT1R-blockers on LV remodeling is mediated through the UPS pathway. In the present study, with the use of cardiac morphometric parameters, haemodynamic measurements and enzyme-linked immunosorbent assay, we demonstrated that post-ischemic HF rats exhibited a significant increase in ventricular remodeling and irbesartan was effective in reversing cardiac remodeling. The expression of TNF-α, ubiquitin protein and 20S proteasome were significantly increased in the MI control group and irbesartan was shown to dose-dependently inhibit the expression of TNF-α, ubiquitin protein and 20S proteasome. In conclusion, it was hypothesized that UPS signaling is involved in ventricular remodeling following MI and the mechanism underlying the effect of irbesartan on ventricular remodeling may be associated with the downregulation of the expression of TNF-α, ubiquitin protein and 20S proteasome.

Keywords: 20S proteasome; heart failure; irbesartan; ubiquitine protein; ventricular remodeling.

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Figures

Figure 1
Figure 1
The effect of irbesartan on myocardial TNF-α content (pg of TNF-α per mg protein) from infarcted rat hearts was demonstrated by ELISA 6 weeks after myocardial infarction (MI). The results are expressed as means ± standard error of the mean. P<0.05 *vs. sham and #vs. MI-control.
Figure 2
Figure 2
The effect of irbesartan on ubiquitin protein plasma concentration was demonstrated by ELISA 6 weeks after myocardial infarction (MI). The results are expressed as means ± standard error of the mean. P<0.05 #vs. sham and *vs. MI-control.
Figure 3
Figure 3
The effect of irbesartan on 20S proteasome plasma concentration was demonstrated by ELISA 6 weeks after myocardial infarction (MI). The results are expressed as means ± standard error of the mean. P<0.05. #vs. sham and *vs. MI-control.
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