2. Academic Validation
  3. Drp1 Promotes Macrophage M1 Polarization and Inflammatory Response in Autoimmune Myocarditis by Driving Mitochondrial Fission

Drp1 Promotes Macrophage M1 Polarization and Inflammatory Response in Autoimmune Myocarditis by Driving Mitochondrial Fission

  • J Cardiovasc Transl Res. 2024 Oct 10. doi: 10.1007/s12265-024-10570-2.
Lin Lin 1,  Jin Wei 2,  Jiahong Xue 2,  Gang Fan 3,  Wenjing Zhu 2,  Yanhe Zhu 4,  Ruiyun Wu 5
Affiliations

Affiliations

  • 1 Department of Cardiovascular Medicine, Cardiovascular Hospital of the Second Affiliated Hospital of Xi'an Jiaotong University, Daminggong Campus, No. 5 Jianqiang Road, Xi'an, 710016, Weiyang District, China. lin_linvas@126.com.
  • 2 Department of Cardiovascular Medicine, Cardiovascular Hospital of the Second Affiliated Hospital of Xi'an Jiaotong University, Daminggong Campus, No. 5 Jianqiang Road, Xi'an, 710016, Weiyang District, China.
  • 3 Second Department of Cardiology, Xianyang First People's Hospital, Shaanxi University of Chinese Medicine, Xianyang, 712000, China.
  • 4 Institute of Endiquidiopathies, School of Public Health, Xi'an Jiaotong University, Xi'an, 710061, China.
  • 5 Department of Internal Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
PMID: 39388091 DOI: 10.1007/s12265-024-10570-2
Abstract

Autoimmune myocarditis (AM) is characterized by an intricate inflammatory response within the myocardium. Dynamin-related protein 1 (Drp1), a pivotal modulator of mitochondrial fission, plays a role in the pathogenesis of various diseases. A myosin-induced experimental autoimmune myocarditis (EAM) mouse model was successfully established. Flow cytometry was employed to detect M1/M2-like macrophages. Mitochondrial fragmentation was assessed using Mito-Tracker Red CMXRos. Drp1 was upregulated and activated in EAM mice. Depletion of Drp1 was observed to mitigate inflammation, macrophage infiltration and M1 polarization within the cardiac tissue of EAM mice. In M1-like macrophages derived from the hearts of EAM mice, Drp1 was found to promote mitochondrial fission and diminish mitochondrial fusion. Furthermore, the depletion of Drp1 reduced the NF-κB-related pro-inflammatory response in EAM-associated M1-like macrophages. Drp1 drives mitochondrial fission in macrophages, driving their M1 polarization and the subsequent inflammatory response. Drp1 may represent an effective target for the prevention and treatment of AM.

Keywords

Autoimmune myocardioptis; Drp1; EAM mouse model; M1 polarization; Mitochondrial fission.

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