Modulating mitochondrial dynamics ameliorates left ventricular dysfunction by suppressing diverse cell death pathways...

Area of Science:

• Cardiovascular Biology
• Mitochondrial Medicine
• Diabetic Complications

Background:

• Diabetic cardiomyopathy (DCM) is linked to altered mitochondrial dynamics, specifically increased fission and reduced fusion.
• This imbalance contributes to cardiomyocyte apoptosis and impaired cardiac function.

Purpose of the Study:

• To investigate the effects of modulating mitochondrial dynamics on DCM in a mouse model.
• To explore the underlying mechanisms of these interventions.

Main Methods:

• DCM was induced in mice, and changes in fission/fusion gene expression were analyzed.
• Mice were treated with Mdivi-1 (fission inhibitor) or Ginsenoside Rg1 (fusion promoter).
• Cardiac function, infarct size, cardiomyocyte apoptosis, and mitochondrial parameters were assessed.

Main Results:

• DCM increased fission genes (Drp1, Mff, Fis1) and decreased fusion genes (Mfn1, Mfn2, Opa1).
• Mdivi-1 and Ginsenoside Rg1 treatments improved cardiac function (LVEF, FS, E/A ratio), reduced infarct size, and decreased apoptosis.
• Mdivi-1 enhanced mitochondrial membrane potential, reduced ROS, and increased ATP; Ginsenoside Rg1 preserved mitochondrial integrity under hypoxia.

Conclusions:

• Restoring mitochondrial dynamics balance by inhibiting fission or promoting fusion shows therapeutic potential for DCM.
• Targeting mitochondrial dynamics offers a promising strategy for mitigating myocardial infarction (MI)-induced cardiac injury.