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
  • 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. [email protected].
  • 5. Institutes of Biomedical Sciences, Fudan University, 131 Dong'an Road, Shanghai, 200032, China. [email protected].
  • 6. Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. [email protected].
  • 7. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. [email protected].
  • 8. Institutes of Biomedical Sciences, Fudan University, 131 Dong'an Road, Shanghai, 200032, China. [email protected].
  • 9. State Key Laboratory of Genetic Engineering, Fudan University, 138 Yixueyuan Road, Shanghai, 200438, China. [email protected].
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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