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Echinacoside reverses myocardial remodeling and improves heart function via regulating SIRT1/FOXO3a/MnSOD axis in HF rats induced by isoproterenol |
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| Authors: | Yajuan Ni Jie Deng Xin Liu Qing Li Juanli Zhang Hongyuan Bai Jingwen Zhang |
| Affiliation: | 1. Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, shaanxi, China;2. Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, shaanxi, China Contribution: Conceptualization (lead), Funding acquisition (equal), Investigation (lead), Methodology (equal), Project administration (equal), Resources (equal), Supervision (lead), Validation (lead), Visualization (equal);3. Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, shaanxi, China Contribution: Conceptualization (equal), Data curation (lead), Formal analysis (equal), Methodology (equal), Project administration (equal), Resources (supporting), Software (lead), Supervision (equal), Validation (equal), Visualization (equal), Writing - original draft (equal), Writing - review & editing (lead);4. Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, shaanxi, China Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (equal), Funding acquisition (supporting), Methodology (equal), Project administration (supporting), Resources (supporting), Software (equal), Validation (supporting), Visualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);5. Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, shaanxi, China Contribution: Project administration (equal), Resources (supporting), Software (supporting);6. Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, shaanxi, China Contribution: Software (supporting), Visualization (equal), Writing - review & editing (lead);7. Department of Cardiology, NHC Key Laboratory on Assisted Circulation of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China Contribution: Conceptualization (supporting), Data curation (equal), Formal analysis (lead), Methodology (lead), Project administration (lead), Validation (equal), Visualization (lead), Writing - original draft (lead) |
| Abstract: | Myocardial remodelling is important pathological basis of HF, mitochondrial oxidative stress is a promoter to myocardial hypertrophy, fibrosis and apoptosis. ECH is the major active component of a traditional Chinese medicine Cistanches Herba, plenty of studies indicate it possesses a strong antioxidant capacity in nerve cells and tumour, it inhibits mitochondrial oxidative stress, protects mitochondrial function, but the specific mechanism is unclear. SIRT1/FOXO3a/MnSOD is an important antioxidant axis, study finds that ECH binds covalently to SIRT1 as a ligand and up-regulates the expression of SIRT1 in brain cells. We hypothesizes that ECH may reverse myocardial remodelling and improve heart function of HF via regulating SIRT1/FOXO3a/MnSOD signalling axis and inhibit mitochondrial oxidative stress in cardiomyocytes. Here, we firstly induce cellular model of oxidative stress by ISO with AC-16 cells and pre-treat with ECH, the level of mitochondrial ROS, mtDNA oxidative injury, MMP, carbonylated protein, lipid peroxidation, intracellular ROS and apoptosis are detected, confirm the effect of ECH in mitochondrial oxidative stress and function in vitro. Then, we establish a HF rat model induced by ISO and pre-treat with ECH. Indexes of heart function, myocardial remodelling, mitochondrial oxidative stress and function, expression of SIRT1/FOXO3a/MnSOD signalling axis are measured, the data indicate that ECH improves heart function, inhibits myocardial hypertrophy, fibrosis and apoptosis, increases the expression of SIRT1/FOXO3a/MnSOD signalling axis, reduces the mitochondrial oxidative damages, protects mitochondrial function. We conclude that ECH reverses myocardial remodelling and improves cardiac function via up-regulating SIRT1/FOXO3a/MnSOD axis and inhibiting mitochondrial oxidative stress in HF rats. |
| Keywords: | echinacoside heart failure mitochondrial oxidative stress myocardial remodelling |