Sex- and age-specific regulation of ACE2: Insights into severe COVID-19 susceptibility

Aged males disproportionately succumb to increased COVID-19 severity, hospitalization, and mortality compared to females. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) facilitate SARS-CoV-2 viral entry and may have sexually dimorphic regulation. As viral load...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 2022-03, Vol.164, p.13-16
Main Authors: Viveiros, Anissa, Gheblawi, Mahmoud, Aujla, Preetinder K., Sosnowski, Deanna K., Seubert, John M., Kassiri, Zamaneh, Oudit, Gavin Y.
Format: Article
Language:English
Subjects:
ACE2
Age
Aging - genetics
Aging - metabolism
Angiotensin-Converting Enzyme 2 - biosynthesis
Angiotensin-Converting Enzyme 2 - genetics
Animals
COVID-19
COVID-19 - epidemiology
Disease Susceptibility
Female
Gene Expression Regulation, Enzymologic
Heart
Heart - virology
Humans
Intestine, Small - enzymology
Intestine, Small - virology
Kidney - enzymology
Kidney - virology
Lung - enzymology
Lung - virology
Male
Mice
Mice, Inbred C57BL
Middle Aged
Myocardium - enzymology
Organ Specificity
Receptors, Virus - biosynthesis
Receptors, Virus - genetics
SARS-CoV-2 - physiology
Serine Endopeptidases - biosynthesis
Serine Endopeptidases - genetics
Sex
Sex Characteristics
TMPRSS2
Young Adult
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Summary:Aged males disproportionately succumb to increased COVID-19 severity, hospitalization, and mortality compared to females. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) facilitate SARS-CoV-2 viral entry and may have sexually dimorphic regulation. As viral load dictates disease severity, we investigated the expression, protein levels, and activity of ACE2 and TMPRSS2. Our data reveal that aged males have elevated ACE2 in both mice and humans across organs. We report the first comparative study comprehensively investigating the impact of sex and age in murine and human levels of ACE2 and TMPRSS2, to begin to elucidate the sex bias in COVID-19 severity. [Display omitted] •Aged males experience increased COVID-19 severity.•SARS-CoV-2 viral load is positively associated with morbidity and mortality.•Tissue levels of viral entry factors may alter susceptibility to severe disease.•ACE2 is differentially expressed across sex and age in mouse and human organs.•Increased severity in aged males may result from increased ACE2 compared to females.
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2021.11.003