Sex differences in mitochondrial gene expression during viral myocarditis

Area of Science:

• Cardiology
• Immunology
• Molecular Biology

Background:

• Myocarditis, an inflammation of the heart muscle, is often triggered by viral infections and subsequent immune responses.
• While sex differences in immune responses to myocarditis are known, the underlying cardiac mechanisms remain unclear.

Approach:

• Investigated sex differences in coxsackievirus B3 (CVB3)-induced myocarditis in male and female BALB/c mice using bulk-tissue RNA-sequencing.
• Performed enrichment analysis to identify transcriptional differences and potential transcription factors driving sex-specific disease patterns.

Key Points:

• Hearts from both male and female mice with myocarditis showed enrichment in innate and adaptive immune response pathways.
• Males with myocarditis displayed enrichment in inflammatory pathways and impaired mitochondrial gene expression.
• Females showed enrichment in mitochondrial respiration and bioenergetics pathways, with higher expression of key regulators like PGC1α, NRF1, and ERRα.

Conclusions:

• Elevated mitochondrial function regulators in female mice with myocarditis may contribute to sex-specific differences in mitochondrial respiratory gene expression.
• These findings suggest a potential mechanism for less severe myocarditis in females following viral infection.