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Danlou Tablet Protects Against Cardiac Remodeling and Dysfunction after Myocardial Ischemia/Reperfusion Injury through Activating AKT/FoxO3a Pathway

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Abstract

Myocardial ischemia/reperfusion injury (I/RI) and ventricular remodeling are the critical pathological basis of heart failure. Danlou tablet (Dan) is a kind of Chinese patent medicine used in angina pectoris treatment in China. However, it remains unclear whether and how Dan could protect against cardiac remodeling after myocardial I/RI. In this study, both preventive and therapeutic administration of Dan attenuated ventricular remodeling and cardiac dysfunction at 3 weeks after myocardial I/RI. Dan inhibited Bax/Bcl2 ratio and Caspase3 cleavage in heart tissues and also inhibited apoptosis of human AC16 cells and neonatal rat cardiomyocytes stressed by oxygen and glucose deprivation/reperfusion. Mechanistically, Dan inhibited myocardial apoptosis through phosphorylating AKT and FoxO3a, thereby inhibiting downstream BIM and PUMA expressions. Collectively, these results demonstrate that Dan treatment is effective to protect against cardiac remodeling and dysfunction after myocardial I/RI and provide theoretical basis for its cardioprotection and clinical application in treating ischemic cardiac diseases.

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All data generated or analysed during this study are included in this article and its supplementary information files.

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Acknowledgements

This work was supported by the grants from National Key Research and Development Program of China (2017YFC1700401 to YB and MZ), National Natural Science Foundation of China (81970335 and 82170285 to YB), and Science and Technology Commission of Shanghai Municipality (22ZR1423100 to JJ, and 23010500300 and 21SQBS00100 to YB).

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Author notes

  1. Lin Li, Weitong Qi, and Yujiao Zhu contributed equally to this work.

Authors and Affiliations

  1. Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China

    Lin Li, Weitong Qi, Yujiao Zhu, Mingming Yin, Chen Chen, Meng Wei, Zhenzhen Huang, Zhuhua Su, Jizong Jiang & Yihua Bei

  2. Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai, 200444, China

    Lin Li, Weitong Qi, Yujiao Zhu, Mingming Yin, Chen Chen, Meng Wei, Zhenzhen Huang, Zhuhua Su, Jizong Jiang & Yihua Bei

  3. Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, ShenyangLiaoning, 110032, China

    Mingxue Zhang

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Contributions

L Li, W Qi, Y Zhu, M Yin, C Chen, M Wei, Z Huang, and Z Su performed the experiments and analyzed the data. M Zhang provided technical assistance. Y Bei and J Jiang designed the study, instructed the experiments and drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jizong Jiang, Mingxue Zhang or Yihua Bei.

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Li, L., Qi, W., Zhu, Y. et al. Danlou Tablet Protects Against Cardiac Remodeling and Dysfunction after Myocardial Ischemia/Reperfusion Injury through Activating AKT/FoxO3a Pathway. J. of Cardiovasc. Trans. Res. 16, 803–815 (2023). https://doi.org/10.1007/s12265-023-10365-x

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