2. Academic Validation
  3. c-FLIP Protects Cardiac Microcirculation in Sepsis-Induced Myocardial Dysfunction Via FUNDC1-Mediated Regulation of Mitochondrial Autophagy

c-FLIP Protects Cardiac Microcirculation in Sepsis-Induced Myocardial Dysfunction Via FUNDC1-Mediated Regulation of Mitochondrial Autophagy

  • JACC Basic Transl Sci. 2025 May 14:101257. doi: 10.1016/j.jacbts.2025.02.016.
Lan Gao 1,  Qindong Shi 1,  Bin Sun 2,  Xiaoyu Zhang 1,  Peiying Zheng 1,  Linjing Zhou 1,  Gang Tian 3,  Hao Li 4
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 2 Department of Critical Care Medicine, Qinghai Provincial People's Hospital, Xining, Qinghai, China.
  • 3 Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: tiangang@xjtu.edu.cn.
  • 4 Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: hao.li215@xjtu.edu.cn.
PMID: 40372306 DOI: 10.1016/j.jacbts.2025.02.016
Abstract

This study investigates the role of c-FLIP in sepsis-induced myocardial dysfunction (SIMD), focusing on cardiac microcirculation and mitochondrial Autophagy. Using SIMD rat and LPS-induced cardiac microvascular endothelial cell injury models, we found that c-FLIP deficiency disrupts mitochondrial homeostasis, exacerbating microcirculatory damage. c-FLIP differentially regulates mitochondrial Autophagy via FUNDC1. Overexpression of c-FLIP balances Autophagy, protects mitochondria, reduces inflammation, and ameliorates SIMD, highlighting its potential as a therapeutic target.

Keywords

FUNDC1; JNK pathway; c-FLIP; cardiac microcirculation; mitochondrial autophagy; sepsis-induced myocardial dysfunction (SIMD).

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