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GDF15 attenuates sepsis-induced myocardial dysfunction by inhibiting cardiomyocytes ferroptosis via the SOCS1/GPX4 signaling pathway.
Li, Xiayun; Sun, He; Zhang, Liyun; Liang, Hongliang; Zhang, Bin; Yang, Jiachang; Peng, Xiangyan; Sun, Jingwei; Zhou, Yang; Zhai, Mengen; Jiang, Liqing; Zhu, Hanzhao; Duan, Weixun.
Afiliação
  • Li X; College of Life Sciences, Northwest University, Xi'an, 710069, China; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China.
  • Sun H; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China.
  • Zhang L; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China.
  • Liang H; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, 94305, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.
  • Zhang B; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China; Department of Surgery, The 954th Hospital of the Chinese People's Liberation Army, Shannan, 856100, China.
  • Yang J; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China.
  • Peng X; School of Medicine, Northwest University, Xi'an, 710069, China.
  • Sun J; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China.
  • Zhou Y; College of Life Sciences, Northwest University, Xi'an, 710069, China.
  • Zhai M; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China.
  • Jiang L; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China. Electronic address: jliqing22@fmmu.edu.cn.
  • Zhu H; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China. Electronic address: zhuhanzhao@fmmu.edu.cn.
  • Duan W; Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical University, Xi'an, 710032, China. Electronic address: duanweix@fmmu.edu.cn.
Eur J Pharmacol ; 982: 176894, 2024 Nov 05.
Article em En | MEDLINE | ID: mdl-39147013
ABSTRACT
Sepsis is a systemic inflammatory response syndrome triggered by infection, presenting with symptoms such as fever, increased heart rate, and low blood pressure. In severe cases, it can lead to multiple organ dysfunction, posing a life-threatening risk. Sepsis-induced cardiomyopathy (SIC) is a critical factor in the poor prognosis of septic patients, leading to myocardial dysfunction characterized by cell death, inflammation, and diminished cardiac function. Ferroptosis, an iron-dependent form of programmed cell death, is a key mechanism causing cardiomyocyte damage in SIC. Growth differentiation factor 15 (GDF15), a member of the TGF-ß superfamily, is associated with various cardiovascular diseases and can inhibit oxidative stress, reduce reactive oxygen species (ROS), and suppress ferroptosis. Elevated serum GDF15 levels in sepsis are correlated with organ injuries, suggesting its potential as a therapeutic target. However, its role and mechanisms in SIC remain unclear. Glutathione peroxidase 4 (GPX4), the only enzyme capable of reducing lipid peroxides within cells, protects cells by reducing lipid peroxidation levels and inhibiting ferroptosis. Investigating the regulatory factors of GPX4 may provide a theoretical basis for SIC treatment. In this study, a mouse SIC model revealed that elevated GDF15 exerts a protective effect. Antagonizing GDF15 exacerbates myocardial damage. Through transcriptomic analysis and other methods, we confirmed that GDF15 inhibits the expression of SOCS1 by activating the ALK5-SMAD2/3 pathway, thereby activates the JAK2/STAT3 pathway, promotes the transcription of GPX4, inhibits ferroptosis in cardiomyocytes, and plays a myocardial protective role in SIC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Sepse / Miócitos Cardíacos / Fator 15 de Diferenciação de Crescimento / Proteína 1 Supressora da Sinalização de Citocina / Ferroptose / Fosfolipídeo Hidroperóxido Glutationa Peroxidase Limite: Animals Idioma: En Revista: Eur J Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Sepse / Miócitos Cardíacos / Fator 15 de Diferenciação de Crescimento / Proteína 1 Supressora da Sinalização de Citocina / Ferroptose / Fosfolipídeo Hidroperóxido Glutationa Peroxidase Limite: Animals Idioma: En Revista: Eur J Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Holanda