Document Type
Article
Publication Date
6-1-2021
Publication Title
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology
Keywords
angiotensin, gonadectomy, heart, kidney, ovariectomy
ISSN
0363-6119
Volume
320
Issue/No.
6
First Page
R925
Last Page
R937
Abstract
Throughout the world, including the United States, men have worse outcomes from COVID-19 than women. SARS-CoV-2, the causative virus of the COVID-19 pandemic, uses angiotensin-converting enzyme 2 (ACE2) to gain cellular entry. ACE2 is a member of the renin-angiotensin system (RAS) and plays an important role in counteracting the harmful effects mediated by the angiotensin type 1 receptor. Therefore, we conducted Ovid MEDLINE and Embase database searches of basic science studies investigating the impact of the biological variable of sex on ACE2 expression and regulation from 2000, the year ACE2 was discovered, through December 31, 2020. Out of 2,131 publications, we identified 853 original research articles on ACE2 conducted in primary cells, tissues, and/or whole mammals excluding humans. The majority (68.7%) of these studies that cited the sex of the animal were conducted in males, while 11.2% were conducted solely in females; 9.26% compared ACE2 between the sexes, while 10.8% did not report the sex of the animals used. General findings are that sex differences are tissue-specific and when present, are dependent upon gonadal state. Renal, cardiac, and adipose ACE2 is increased in both sexes under experimental conditions that model co-morbidities associated with worse COVID-19 outcomes including hypertension, obesity, and renal and cardiovascular diseases; however, ACE2 protein was generally higher in the males. Studies in knockout mice indicate ACE2 plays a greater role in protecting the female from developing hypertension than the male. Studying the biological variable of sex in ACE2 research provides an opportunity for discovery in conditions involving RAS dysfunction and will shed light on sex differences in COVID-19 severity.
NSUWorks Citation
Miličić Stanić, Branka; Maddox, Sydney; de Souza, Aline M.; Wu, Xie; Mehranfard, Danial; Ji, Hong; Speth, Robert C.; and Sandberg, Kathryn, "Male bias in ACE2 basic science research: missed opportunity for discovery in the time of COVID-19" (2021). HPD Articles. 45.
https://nsuworks.nova.edu/hpd_facarticles/45
ORCID ID
0000-0002-6434-2136
DOI
10.1152/ajpregu.00356.2020
Copyright
Copyright © 2021 the American Physiological Society
