title: Chronic aspirin via dose-dependent and selective inhibition of cardiac proteasome possibly contributed a potential risk to the ischemic heart.
abstract: Impaired cardiac proteasome has been reported in ischemic heart and heart failure. Recent data highlighted aspirin as an inhibitor of the ubiquitin-proteasome system, however, it's unclear whether it affects cardiac proteasome functions. Myocardial infarction (MI), sham or normal male SD rats were injected intraperitoneally with high (300 mg/kg), low (5 mg/kg) aspirin or saline (control) once a day for seven weeks. Parallel experiments were performed in the hypoxia/reoxygenated human ventricular myocytes. Dose-related increases in heart and ventricular weight, and impaired cardiac functions, were found more exacerbated in the aspirin-treated MI rat hearts than the saline-treated MI counterparts. The activity of 26S, 20S and 19S declined by about 30%, or the 20S proteasome subunits β5, β2 and β1 decreased by 40%, 20% and 30%, respectively, in the MI rats compared with the non-MI rats (P<0.05). Compared with the saline-treated MI rats, 26S and 20S in high or low dose aspirin-treated MI rats further decreased by 30% and 20%, β5 by 30% and 12%, and β1 by 40% and 30%, respectively, and the lost activity was correlated with the compromised cardiac functions or the decreased cell viability. The dose-related and selective inhibition of 26S and 20S proteasome, or the 20S proteasome subunits β5 and β1 by aspirin was comparable to their protein expressions in the MI rats and in the cultured cells. The impaired cardiac proteasome, enhanced by chronic aspirin treatment, attenuated the removal of oxidative and ubiquitinated proteins, and chronic aspirin treatment via selective and dose-dependent inhibition of cardiac proteasome possibly constituted a potential risk to ischemic heart.
authors.affiliation: Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fujian, China. tchunj@126.com
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Tan
authors.forename: Wenlie
authors.initials: W
authors.lastname: Chen
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Wu
authors.forename: Jiumao
authors.initials: J
authors.lastname: Lin
authors.forename: Ruhui
authors.initials: R
authors.lastname: Lin
authors.forename: Xuerui
authors.initials: X
authors.lastname: Tan
authors.forename: Songming
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000453:epidemiology* / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000502:physiology*; D061988:Proteasome Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors
chemical_list: D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex; D001241:Aspirin
keywords: A potential risk; Aspirin; Cardiac proteasome; Ischemic rat heart; Selective inhibition