Qiliqiangxin Protects Against Cardiac Ischemia-Reperfusion Injury via Activation of the mTOR Pathway

Abstract

Background/Aims: Qiliqiangxin (QL) has been used for the treatment of chronic heart failure in China. Accumulating evidence suggests QL's cardio-protective effects on continuous myocardial ischemia. However, it is unclear whether QL has beneficial effects on cardiac ischemia-reperfusion (I/R) injury. Methods: A mouse model of cardiac I/R was established by ligation of the left anterior descending coronary artery for 45 minutes followed by reperfusion. The mice were treated with QL for three days before surgery and continually after I/R. Triphenyltetrazolium chloride staining, echocardiography and Masson's trichrome staining were used to determine infarct size, cardiac function, and fibrosis, respectively. Expression levels of phospho-mTOR (Ser2448), mTOR, phospho-4EBP (Ser65), 4EBP, phospho-Akt (Ser473) and Akt were detected by Western blotting. Results: At 1 day after I/R, QL treatment significantly reduced the infarct size of mice exposed to I/R. At 7 days after I/R, mortality was reduced in QL treated animals in comparison with the control group. In addition, QL treated mice showed increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at 1 and 7 days after I/R. In agreement, Masson's trichrome staining demonstrated that interstitial fibrosis was less pronounced in QL treated mice compared with controls, suggesting that adverse left ventricular remodeling is attenuated in QL treated mice. Moreover, western blotting analysis demonstrated that QL activated the mTOR pathway, while mTOR inhibition via Rapamycin abolished the protective effects of QL against I/R injury. Conclusion: This study suggests that QL attenuates the progression of cardiac remodeling after I/R likely via mTOR activation. This represents a new application for QL in the prevention of I/R injury.

Choline Inhibits Ischemia-Reperfusion-Induced Cardiomyocyte Autophagy in Rat Myocardium by Activating Akt/mTOR Signaling

“…The dosage of rapamycin (5 mg/kg, ip) in this study was referred to previous studies [36, 37]. And it was noted that the dosage of rapamycin range from 0.25 mg/kg to 5 mg/kg in previous studies.…”

The Metabolic Effects of Traditional Chinese Medication Qiliqiangxin on H9C2 Cardiomyocytes

“…Emerging evidence suggest that mitochondrial dysfunction may lead to the genesis of heart failure, which indicates a close association between mitochondrial biogenesis and cardiac function [21][22][23]. We previously reported the protective effects of traditional Chinese medicine QLQX on cardiomyocyte energy metabolism in mice with acute myocardial infarction or cardiac ischemia-reperfusion injury [2,24]. To better understand the effect of QLQX on physiological mitochondrial metabolism, we treated H9C2 cells with QLQX and examined oxidative metabolism/glycolysis by XF96 analyzer.…”

“…To investigate the effects of QLQX on H9C2 cell metabolism, we treated cells with incremental concentrations (0.25, 0.5, and 1.0 μg/mL) and durations (6,12,24, and 48 hours) of QLQX. QLQX from 0.5 μg/mL increased basal oxygen consumption rate (OCR) following 48 hour treatment (Fig.…”

Inhibition of Mir-128-3p by Tongxinluo Protects Human Cardiomyocytes From Ischemia/Reperfusion Injury via Upregulation of P70s6k1/P-P70s6k1

“…It was estimated that reperfusion can reduce myocardial infarct size by 40%, while a proportion of the remaining 30% infarct volume results from MIRI and, theoretically, is avoidable (Yellon and Hausenloy, 2007). Activation of the Reperfusion Injury Salvage Kinase (RISK) Pathway by pharmacological (Gao et al, 2002;Kis et al, 2003a;Gross et al, 2004;Tissier et al, 2007;Penna et al, 2012;Zhou et al, 2015) or non-pharmacological (Juhaszova et al, 2004;Tsang et al, 2004;Hausenloy et al, 2005;Zhu M. et al, 2006;Jin et al, 2008) stimulation was shown in dozens of preclinical studies to reduce the size of myocardial infarcts resulting from reperfusion injury. Therefore, pharmacological agents that activate the RISK associated kinases might have powerful cardioprotective properties.…”