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Drp1 Promotes Macrophage M1 Polarization and Inflammatory Response in Autoimmune Myocarditis by Driving Mitochondrial
Lin Lin1, Jin Wei2, Jiahong Xue2
1Department 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.
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.
Insights
Dynamin-related protein 1 (Drp1) drives inflammation in autoimmune myocarditis by promoting mitochondrial fission in macrophages. Inhibiting Drp1 reduces cardiac inflammation and may offer a therapeutic target for this condition.
Area of Science:
- Cardiovascular Biology
- Immunology
- Mitochondrial Biology
Background:
- Autoimmune myocarditis (AM) involves complex myocardial inflammation.
- Dynamin-related protein 1 (Drp1) regulates mitochondrial fission and disease pathogenesis.
Purpose of the Study:
- To investigate the role of Drp1 in myosin-induced experimental autoimmune myocarditis (EAM).
- To determine if Drp1 inhibition can mitigate cardiac inflammation and macrophage polarization in EAM.
Main Methods:
- Established a myosin-induced EAM mouse model.
- Utilized flow cytometry for macrophage analysis and Mito-Tracker Red CMXRos for mitochondrial assessment.
- Assessed Drp1 expression, activation, and its impact on mitochondrial dynamics and NF-κB signaling.
Main Results:
- Drp1 was upregulated and activated in EAM mice.
- Drp1 depletion reduced cardiac inflammation, macrophage infiltration, and M1 polarization.
- Drp1 promoted mitochondrial fission and diminished fusion in M1-like macrophages from EAM hearts.
- Drp1 inhibition decreased NF-κB-related pro-inflammatory responses in these macrophages.
Conclusions:
- Drp1 drives mitochondrial fission in macrophages, promoting M1 polarization and subsequent inflammation in autoimmune myocarditis.
- Drp1 inhibition presents a potential therapeutic strategy for preventing and treating autoimmune myocarditis.
