Chronic mitochondrial dynamic-targeted therapy alleviates left ventricular dysfunction by reducing multiple
Chanon Piamsiri1, Chayodom Maneechote2, Kewarin Jinawong1
1Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
European Journal of Pharmacology
|June 15, 2024
Summary
Targeting mitochondrial dynamics with Mdivi-1 or M1 improved heart function after myocardial infarction (MI). These therapies reduced cell death and pathological remodeling, offering new cardioprotective strategies for MI recovery.
Area of Science:
- Cardiovascular Research
- Mitochondrial Biology
- Cell Death Pathways
Background:
- Mitochondrial dysfunction and programmed cell death (PCD) worsen myocardial infarction (MI) outcomes.
- Mitochondrial dynamics modulators (fusion promoter M1, fission inhibitor Mdivi-1) show cardioprotection, but their role post-MI is unexplored.
Purpose of the Study:
- To investigate the therapeutic potential of targeting mitochondrial dynamics in a rat model of myocardial infarction.
- To evaluate the effects of M1 and Mdivi-1 on cardiac function, mitochondrial health, and cell death pathways post-MI.
Main Methods:
- A permanent left-anterior descending (LAD) coronary artery occlusion model was used in rats.
- Post-MI rats received vehicle, enalapril, Mdivi-1, or M1 for 32 days.
- Cardiac/mitochondrial function, histopathology, and molecular markers of cell death were assessed.
Main Results:
- Enalapril, Mdivi-1, and M1 treatments significantly reduced cardiac remodeling and myocardial injury.
- All interventions improved left ventricular (LV) function in post-MI rats.
- Treatments attenuated mitochondrial dynamic imbalance and suppressed apoptosis, necroptosis, and pyroptosis.
Conclusions:
- Chronic therapy targeting mitochondrial dynamics (Mdivi-1, M1) mitigates mitochondrial dysfunction and PCD activation post-MI.
- This approach leads to improved cardiac function and reduced pathological remodeling in a post-MI setting.
- Mitochondrial dynamic modulation represents a promising therapeutic strategy for myocardial infarction.
