2. Academic Validation
  3. Bufalin Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Macrophage Pyroptosis via P62 Pathway

Bufalin Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Macrophage Pyroptosis via P62 Pathway

  • J Cardiovasc Transl Res. 2024 Dec 28. doi: 10.1007/s12265-024-10577-9.
Chang Li 1,  Zhen Ma 2,  Xiang Wei 3,  Ying Wang 1,  Jian Wu 1,  Xuan Li 1,  Xiaolei Sun 1,  Zhiwen Ding 4 5,  Cheng Yang 6,  Yunzeng Zou 7 8 9
Affiliations

Affiliations

  • 1 Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
  • 2 Institutes of Biomedical Sciences, Fudan University, 131 Dong'an Road, Shanghai, 200032, China.
  • 3 Department of Cardiology, Shanghai Fifth People's Hospital, Fudan University, 128 Ruili Road, Shanghai, 200032, China.
  • 4 Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. zhiwen_d@fudan.edu.cn.
  • 5 Institutes of Biomedical Sciences, Fudan University, 131 Dong'an Road, Shanghai, 200032, China. zhiwen_d@fudan.edu.cn.
  • 6 Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. yang.cheng@zs-hospital.sh.cn.
  • 7 Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. zou.yunzeng@zs-hospital.sh.cn.
  • 8 Institutes of Biomedical Sciences, Fudan University, 131 Dong'an Road, Shanghai, 200032, China. zou.yunzeng@zs-hospital.sh.cn.
  • 9 State Key Laboratory of Genetic Engineering, Fudan University, 138 Yixueyuan Road, Shanghai, 200438, China. zou.yunzeng@zs-hospital.sh.cn.
PMID: 39733202 DOI: 10.1007/s12265-024-10577-9
Abstract

Bufalin, which is isolated from toad venom, exerts positive effects on hearts under pathological circumstance. We aimed to investigate the effects and mechanisms of bufalin on myocardial I/R injury. In vivo, bufalin ameliorated myocardial I/R injury, which characteristics with better ejection function, decreased infarct size and less Apoptosis. The levels of pyroptotic proteins were increased in I/R-treated macrophages and inflammatory cytokines expressed more in I/R-induced mouse, which could be attenuated by bufalin. Bufalin also reduced H/R-treated macrophage Pyroptosis in vitro. Autophagic flux blockage and ROS accumulation were reduced by bufalin in impaired macrophages. Overexpression of p62 abrogated the anti-proptosis and anti-oxidative effects of bufalin. The levels of Apoptosis related proteins were changed and TUNEL-positive ratio was raised in cardiomyocytes that received conditioned medium treatment with H/R-treated macrophages, while bufalin pretreatment could reduce Apoptosis. These findings indicate that bufalin may attenuate myocardial I/R injury by suppressing macrophage Pyroptosis via p62 pathway.

Keywords

Bufalin; Macrophage; Myocardial ischemia/reperfusion injury; P62; Pyroptosis.

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