title: Inhibition of ubiquitin protein expression and 20S proteasome activity by irbesartan prevents post-infarction ventricular remodeling and decreases TNF-α generation.
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.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Naiju
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Cardiovasology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Tianping
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Cardiovasology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Cardiovasology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Bi
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Pharmacy, Bengbu Second People's Hospital, Bengbu, Anhui 233000, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Nie
authors.affiliation: Department of Pharmacy, Bengbu Second People's Hospital, Bengbu, Anhui 233000, P.R. China.
authors.forename: Huiling
authors.initials: H
authors.lastname: An
authors.affiliation: Department of Pharmacy, Bengbu Second People's Hospital, Bengbu, Anhui 233000, P.R. China.
authors.forename: Duilan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Bengbu Second People's Hospital, Bengbu, Anhui 233000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Yu
keywords: 20S proteasome; heart failure; irbesartan; ubiquitine protein; ventricular remodeling