title: Exogenous NAD(+) administration significantly protects against myocardial ischemia/reperfusion injury in rat model.
abstract: Acute myocardial infarction is one of the leading causes for death around the world. Although essential for successful interventional therapy, it is inevitably complicated by reperfusion injury. Thus effective approaches to reduce ischemia/reperfusion (I/R) injury are still critically needed. To test our hypothesis that intravenous administration of NAD(+) can attenuate I/R injury by reducing apoptotic damage and enhancing antioxidant capacity, we used a rat mode of myocardial I/R. Our study found that administration of 10-20 mg/kg NAD(+) can dose dependently reduce myocardial infarct induced by I/R, with an approximately 85% reduction of the infarct at the dosage of 20 mg/kg NAD(+). We further found that the injection of NAD(+) can significantly decrease I/R-induced apoptotic damage in the heart: NAD(+) administration can both decrease the TUNEL signals, Bax, cleaved caspase-3 levels and increase the Bcl-XL levels in the rats that are subjected to myocardial I/R injury. NAD(+) administration can also significantly attenuate I/R-induced decreases in SOD activity and SOD-2 protein levels in the hearts. NAD(+) can profoundly decrease myocardial I/R injury at least partially by attenuating apoptotic damage and enhancing the antioxidant capacity, thus suggesting that NAD(+) may become a promising therapeutic agent for myocardial I/R injury.
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University 241 West Huaihai Road, Shanghai 200030, P.R. China.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University 1954 Huashan Road, Shanghai 200030, P.R. China.
authors.forename: Ban
authors.initials: B
authors.lastname: Wang
authors.affiliation: Jiangsu University Health Science Center 3 Yizheng Road, Zhenjiang, Jiangsu, 212001, P.R. China.
authors.forename: Xingli
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University 241 West Huaihai Road, Shanghai 200030, P.R. China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University 241 West Huaihai Road, Shanghai 200030, P.R. China.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Han
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University 1954 Huashan Road, Shanghai 200030, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University 241 West Huaihai Road, Shanghai 200030, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gan
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University 241 West Huaihai Road, Shanghai 200030, P.R. China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University 1954 Huashan Road, Shanghai 200030, P.R. China.
authors.forename: Weihai
authors.initials: W
authors.lastname: Ying
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University 241 West Huaihai Road, Shanghai 200030, P.R. China.
authors.forename: Xinkai
authors.initials: X
authors.lastname: Qu
keywords: Myocardial ischemia/reperfusion; NAD+; antioxidation; apoptosis; infarction