ArticleBiology of sex differences2024
Sex differences in mitochondrial gene expression during viral myocarditis.
Article in Biology of sex differences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Sex differences in a mouse model of radiation-induced cardiotoxicity.Research square · 2026Article
- Cardiac Mitochondrial Dysfunction Following Bleomycin-Induced Acute Lung Injury in Rats.bioRxiv : the preprint server for biology · 2026Article
- Sex matters: mechanistic insights into sex-driven patterns of autoimmunity and implications for pharmacotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Global epidemiology of myocarditis: disparities in age, sex and geography.Nature reviews. Cardiology · 2026Review
- The role of glucose metabolic reprogramming in myocarditis and advances in therapeutic strategies.Frontiers in cardiovascular medicine · 2026Review
- PGC-1α: key regulator of mitochondrial biogenesis and cellular differentiation in metabolic and regenerative tissues.Cell & bioscience · 2025Review
- Sex differences in cardiac sarcoidosis.International journal of cardiology. Heart & vasculature · 2025Article
- Transcriptomic analysis of coxsackievirus B3 infection in induced pluripotent stem cell-derived brain-like endothelial cells.Journal of virology · 2025Article
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27 authors.
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Abstract
backgroundMyocarditis is an inflammation of the heart muscle most often caused by viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood.
methodsMale and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis. We performed enrichment analysis and functional validation to understand sex differences in the transcriptional landscape of myocarditis and identify factors that might drive sex differences in myocarditis.
resultsAs expected, the hearts of male and female mice with myocarditis were significantly enriched for pathways related to an innate and adaptive immune response compared to uninfected controls. Unique to this study, we found that males were enriched for inflammatory pathways and gene changes that suggested worse mitochondrial electron transport function while females were enriched for pathways related to mitochondrial homeostasis. Mitochondria isolated from the heart of males were confirmed to have worse mitochondrial respiration than females during myocarditis. Unbiased TRANSFAC analysis identified estrogen-related receptor alpha (ERRα) as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis. Transcript and protein levels of ERRα were confirmed as elevated in females with myocarditis compared to males. Differential binding analysis from chromatin immunoprecipitation (ChIP) sequencing confirmed that ERRα bound highly to select predicted respiratory chain genes in females more than males during myocarditis.
conclusionsFemales with viral myocarditis regulate mitochondrial homeostasis by upregulating master regulators of mitochondrial transcription including ERRα.
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