Abstract Background Myocarditis 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. Methods Male 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. Results As 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. Conclusions Females with viral myocarditis regulate mitochondrial homeostasis by upregulating master regulators of mitochondrial transcription including ERRα.

Damian N. Di Florio

Gabriel J. Weigel

David J. Gorelov

Elizabeth J. McCabe

Danielle J. Beetler

Katie A. Shapiro

Katelyn A. Bruno

Isha Chekuri

Angita Jain

Emily R. Whelan

Gary R. Salomon

Sami Khatib

Natalie E. Bonvie-Hill

Jessica J. Fliess

Presley G. Giresi

Charwan Hamilton

Cameron J. Hartmoyer

Varsini Balamurugan

Ashley A. Darakjian

Brandy H. Edenfield

S. Christian Kocsis

Christopher J. McLeod

Leslie T. Cooper

Étienne Audet-Walsh

Michael J. Coronado

Jon Sin

DeLisa Fairweather

Biology of Sex Differences

与任何其他科学期刊不同，《性别差异生物学》侧重于生理、行为和疾病方面的性别差异，从分子到表型，并结合了基础和临床研究。该杂志旨在提高对基本原则的理解，并促进针对性别差异的治疗和诊断工具的开发。这本开放获取期刊是性别差异研究组织备受推崇的官方期刊，由女性健康研究协会共同出版。主题领域包括但不限于以下方面的性别差异：基因组学；微生物组；表观遗传学；分子和细胞生物学；组织生物学；生理;任何系统中的组织系统的相互作用，包括脂肪、行为、心血管、免疫、肌肉、神经、肾脏和骨骼；关于疾病性别差异或对治疗反应的临床研究

The journal "Biology of Sex Differences" is a unique scientific publication that focuses on sex differences in physiology, behavior, and disease, spanning from molecular to phenotypic levels, and integrating both basic and clinical research. The journal aims to enhance the understanding of fundamental principles related to sex differences and to promote the development of targeted diagnostic and therapeutic tools. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences, co-published by the Society for Women's Health Research. The thematic areas covered include, but are not limited to, sex differences in genomics, microbiomics, epigenetics, molecular and cellular biology, tissue biology, physiology, and the interactions of organizational systems in various systems, including adipose, behavioral, cardiovascular, immune, muscular, neurological, renal, and skeletal systems; as well as clinical research on disease sex differences or responses to treatment.

《Biology of Sex Differences》是一份独特的科学期刊，专注于生理、行为和疾病方面的性别差异，涵盖从分子到表型的各个层面，并结合基础与临床研究。该期刊旨在加深对性别差异基本原则的理解，并促进针对这些差异的治疗和诊断工具的开发。作为一份开放获取的期刊，它是性别差异研究组织的官方期刊，由女性健康研究协会共同出版。期刊的主题领域包括但不限于以下方面的性别差异：基因组学、微生物组、表观遗传学、分子与细胞生物学、组织生物学、生理学，以及在不同系统中组织系统的相互作用，包括脂肪、行为、心血管、免疫、肌肉、神经、肾脏和骨骼等；同时也涵盖关于疾病性别差异或对治疗反应的临床研究。

Sex differences in mitochondrial gene expression during viral myocarditis

病毒性心肌炎中线粒体基因表达的性别差异

Category	Quartile
医学	2
医学, 内分泌学与代谢	2
医学, 遗传学	2

Sex differences in mitochondrial gene expression during viral myocarditis

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Journal Info

Category	Quartile
GENETICS & HEREDITY	1