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

Anissa Viveiros; Mahmoud Gheblawi; Preetinder K Aujla; Deanna K Sosnowski; John M Seubert; Zamaneh Kassiri; Gavin Y Oudit

doi:10.1016/j.yjmcc.2021.11.003

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

J Mol Cell Cardiol. 2022 Mar:164:13-16. doi: 10.1016/j.yjmcc.2021.11.003. Epub 2021 Nov 11.

Authors

Anissa Viveiros¹, Mahmoud Gheblawi², Preetinder K Aujla², Deanna K Sosnowski³, John M Seubert⁴, Zamaneh Kassiri², Gavin Y Oudit⁵

Affiliations

¹ Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
² Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
³ Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
⁴ Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada; Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
⁵ Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address: gavin.oudit@ualberta.ca.

Abstract

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.

Keywords: ACE2; Age; COVID-19; Heart; Sex; TMPRSS2.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Aging / genetics
Aging / metabolism*
Angiotensin-Converting Enzyme 2 / biosynthesis*
Angiotensin-Converting Enzyme 2 / genetics
Animals
COVID-19 / epidemiology*
Disease Susceptibility
Female
Gene Expression Regulation, Enzymologic*
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 Characteristics*
Young Adult

Substances

Receptors, Virus
ACE2 protein, human
Ace2 protein, mouse
Angiotensin-Converting Enzyme 2
Serine Endopeptidases
TMPRSS2 protein, human
TMPRSS2 protein, mouse

Grants and funding

CIHR/Canada