Sex differences in mitochondrial gene expression during viral myocarditis

被引：0

作者：

Di Florio, Damian N. ^{[1
,2
,3
]}

Weigel, Gabriel J. ^{[1
]}

Gorelov, David J. ^{[1
]}

Mccabe, Elizabeth J. ^{[1
]}

Beetler, Danielle J. ^{[1
,2
,3
]}

Shapiro, Katie A. ^{[1
]}

Bruno, Katelyn A. ^{[1
,4
]}

Chekuri, Isha ^{[1
]}

Jain, Angita ^{[1
]}

Whelan, Emily R. ^{[1
,2
,3
]}

Salomon, Gary R. ^{[1
]}

Khatib, Sami ^{[1
]}

Bonvie-Hill, Natalie E. ^{[1
]}

Fliess, Jessica J. ^{[1
]}

Giresi, Presley G. ^{[1
]}

Hamilton, Charwan ^{[1
]}

Hartmoyer, Cameron J. ^{[1
]}

Balamurugan, Varsini ^{[1
]}

Darakjian, Ashley A. ^{[1
]}

Edenfield, Brandy H. ^{[5
]}

Kocsis, S. Christian ^{[1
]}

Mcleod, Christopher J. ^{[1
]}

Cooper, Leslie T. ^{[1
]}

Audet-Walsh, Etienne ^{[6
]}

Coronado, Michael J. ^{[7
]}

Sin, Jon ^{[8
]}

Fairweather, Delisa ^{[1
,2
,9
,10
]}

机构：

[1] Mayo Clin, Dept Cardiovasc Med, Jacksonville, FL 32224 USA

[2] Mayo Clin, Ctr Clin & Translat Sci, Rochester, MN 32224 USA

[3] Mayo Clin, Grad Sch Biomed Sci, Jacksonville, FL 32224 USA

[4] Univ Florida, Div Cardiovasc Med, Dept Med, Gainesville, FL USA

[5] Mayo Clin Jacksonville, Dept Canc Biol, Jacksonville, FL 32224 USA

[6] Univ Laval, Endocrinol Nephrol Res Div, CHU Quebec, Res Ctr, Quebec City, PQ, Canada

[7] Cytokinetics Inc, South San Francisco, CA USA

[8] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL USA

[9] Mayo Clin, Dept Immunol, Jacksonville, FL 32224 USA

[10] Mayo Clin, Dept Med, Jacksonville, FL 32224 USA

来源：

BIOLOGY OF SEX DIFFERENCES | 2024年 / 15卷 / 01期

关键词：

Inflammation; Innate immunity; Coxsackievirus B3; Estrogen-related receptor alpha/ERR alpha; Mitochondria; Electron transport chain; ChIP; ESTROGEN-RELATED RECEPTOR; COXSACKIEVIRUS B3-INDUCED MYOCARDITIS; ERR-ALPHA; ENERGY-EXPENDITURE; IFN-GAMMA; ACTIVATION; ORPHAN; COACTIVATOR; INFECTION; INTERLEUKIN-1-BETA;

D O I：

10.1186/s13293-024-00678-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (ERR alpha) as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis. Transcript and protein levels of ERR alpha were confirmed as elevated in females with myocarditis compared to males. Differential binding analysis from chromatin immunoprecipitation (ChIP) sequencing confirmed that ERR alpha 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 ERR alpha.

引用

页数：27

共 50 条

[21] Sex differences in survival and mitochondrial bioenergetics during aging in Drosophila
Ballard, J. William O.
Melvin, Richard G.
Miller, Joseph T.
Katewa, Subhash D.
AGING CELL, 2007, 6 (05) : 699 - 708
[22] DETERMINANTS OF GENE EXPRESSION DURING VIRAL DEVELOPMENT
GEIDUSCHEK, EP
WILSON, DL
GAGE, LP
JOURNAL OF CELLULAR PHYSIOLOGY, 1969, 74 (2P2S) : 81 - +
[23] Murine heart gene expression during acute Chagasic myocarditis
Henao-Martinez, Andres F.
Parra-Henao, Gabriel
GENOMICS DATA, 2015, 4 : 76 - +
[24] Sex differences in coronavirus disease 2019 myocarditis
Beetler, Danielle J.
Fairweather, DeLisa
CURRENT OPINION IN PHYSIOLOGY, 2023, 35
[25] Sex differences in ICI myocarditis: Hormones to the rescue
Nguyen, Patricia K.
Wu, Sean M.
SCIENCE TRANSLATIONAL MEDICINE, 2022, 14 (669)
[26] Sex and Gender Differences in Myocarditis and Dilated Cardiomyopathy
Fairweather, DeLisa
Cooper, Leslie T., Jr.
Blauwet, Lori A.
CURRENT PROBLEMS IN CARDIOLOGY, 2013, 38 (01) : 7 - 46
[27] Estrogen receptor-alpha gene expression in the cortex: Sex differences during development and in adulthood
Wilson, Melinda E.
Westberry, Jenne M.
Trout, Amanda L.
HORMONES AND BEHAVIOR, 2011, 59 (03) : 353 - 357
[28] Sex differences in kidney gene expression during the life cycle of F344 rats
Joshua C Kwekel
Varsha G Desai
Carrie L Moland
Vikrant Vijay
James C Fuscoe
Biology of Sex Differences, 4
[29] Sex differences in kidney gene expression during the life cycle of F344 rats
Kwekel, Joshua C.
Desai, Varsha G.
Moland, Carrie L.
Vijay, Vikrant
Fuscoe, James C.
BIOLOGY OF SEX DIFFERENCES, 2013, 4
[30] Sex differences in mitochondrial functions
Cogliati, Sara
ACTA PHYSIOLOGICA, 2024, 240 : 19 - 19

← 1 2 3 4 5 →