Jing Liu1, Yongfei Ai1, Xiaolin Niu1, Fujun Shang1, Zhili Li1, Hui Liu1, Wei Li1, Wenshuai Ma1, Ruirui Chen1, Ting Wei1, Xue Li2, Xiaoli Li3. 1. Department of Cardiology, Tangdu Hospital, AIR FORCE Medical University, 1 Xinsi Road, Xi'an, Shaanxi, 710038, China. 2. Department of Cardiology, Tangdu Hospital, AIR FORCE Medical University, 1 Xinsi Road, Xi'an, Shaanxi, 710038, China. Electronic address: lxhlms@126.com. 3. Department of Cardiology, Tangdu Hospital, AIR FORCE Medical University, 1 Xinsi Road, Xi'an, Shaanxi, 710038, China. Electronic address: lixiaoli2401@163.com.
Abstract
BACKGROUND: Heart failure (HF) is an epidemic disease with increased incidence annually. It has been reported that taurine can improve cardiac function. This study investigated the cardioprotective effects of taurine in pressure-loaded HF mice and elucidated the possible mechanism. METHODS: HF models were established by transverse aortic constriction (TAC). Animals were treated with either taurine for 9 weeks and/or the SIRT1 inhibitor EX527 (5 mg/kg/day, every 2days) after TAC operation. Cardiac function and geometry were revealed by echocardiography. Myocardial hypertrophy and fibrosis were assessed using Fluorescent wheat germ agglutinin (WGA) staining and Masson's trichrome staining. Western blot and RT-PCR were performed to elucidate the expression of target proteins and genes respectively. Apoptosis in cardiomyocytes was detected by TUNEL staining. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD) and malonyldialdehyde (MDA) and reactive oxygen species (ROS). Taurine concentrations and NAD+/NADH ratio were determined by taurine and NAD+/NADH assay kit. RESULTS: Taurine notably relieved cardiac dysfunction after TAC. The mechanisms were attributed to reduced myocyte hypertrophy and fibrosis, and alleviated apoptosis and oxidative stress. Meanwhile, taurine increased NAD+/NADH ratio，promoted the expression of SIRT1 and suppressed p53 acetylation. However, EX-527(inhibitor of SIRT1) decreased NAD+/NADH ratio and increased acetyl-p53 levels, and abolished the cardioprotective effects of taurine on mice subjected to TAC and increased apoptosis and oxidative stress. CONCLUSION: The mechanism responsible for cardiac-protective effects of taurine in HF induced by pressure overload is associated with the activation of the SIRT1-p53 pathway.
BACKGROUND:Heart failure (HF) is an epidemic disease with increased incidence annually. It has been reported that taurine can improve cardiac function. This study investigated the cardioprotective effects of taurine in pressure-loaded HFmice and elucidated the possible mechanism. METHODS:HF models were established by transverse aortic constriction (TAC). Animals were treated with either taurine for 9 weeks and/or the SIRT1 inhibitor EX527 (5 mg/kg/day, every 2days) after TAC operation. Cardiac function and geometry were revealed by echocardiography. Myocardial hypertrophy and fibrosis were assessed using Fluorescent wheat germ agglutinin (WGA) staining and Masson's trichrome staining. Western blot and RT-PCR were performed to elucidate the expression of target proteins and genes respectively. Apoptosis in cardiomyocytes was detected by TUNEL staining. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD) and malonyldialdehyde (MDA) and reactive oxygen species (ROS). Taurine concentrations and NAD+/NADH ratio were determined by taurine and NAD+/NADH assay kit. RESULTS:Taurine notably relieved cardiac dysfunction after TAC. The mechanisms were attributed to reduced myocyte hypertrophy and fibrosis, and alleviated apoptosis and oxidative stress. Meanwhile, taurine increased NAD+/NADH ratio，promoted the expression of SIRT1 and suppressed p53 acetylation. However, EX-527(inhibitor of SIRT1) decreased NAD+/NADH ratio and increased acetyl-p53 levels, and abolished the cardioprotective effects of taurine on mice subjected to TAC and increased apoptosis and oxidative stress. CONCLUSION: The mechanism responsible for cardiac-protective effects of taurine in HF induced by pressure overload is associated with the activation of the SIRT1-p53 pathway.
Authors: Stella Baliou; Maria Adamaki; Petros Ioannou; Aglaia Pappa; Mihalis I Panayiotidis; Demetrios A Spandidos; Ioannis Christodoulou; Anthony M Kyriakopoulos; Vassilis Zoumpourlis Journal: Mol Med Rep Date: 2021-06-29 Impact factor: 2.952