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Published in: Clinical Hypertension 1/2020

Open Access 01-12-2020 | COVID-19 | Letter to the Editor

The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms

Author: Craig Steven McLachlan

Published in: Clinical Hypertension | Issue 1/2020

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Abstract

There is current debate concerning the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs), for hypertension management, during COVID-19 infection. Specifically, the suggestion has been made that ACE inhibitors or ARBs could theoretically contribute to infection via increasing ACE2 receptor expression and hence increase viral load. The ACE2 receptor is responsible for binding the SAR-CoV2 viral spike and causing COVID-19 infection. What makes the argument somewhat obtuse for ACE inhibitors or ARBs is that ACE2 receptor expression can be increased by compounds that activate or increase the expression of SIRT1. Henceforth common dietary interventions, vitamins and nutrients may directly or indirectly influence the cellular expression of the ACE2 receptor. There are many common compounds that can increase the expression of the ACE2 receptor including Vitamin C, Metformin, Resveratrol, Vitamin B3 and Vitamin D. It is important to acknowledge that down-regulation or blocking the cellular ACE2 receptor will likely be pro-inflammatory and may contribute to end organ pathology and mortality in COVID-19. In conclusion from the perspective of the ACE2 receptor, COVID-19 prevention and treatment are distinctly different. This letter reflects on this current debate and suggests angiotensin-converting enzyme inhibitors and ARBs are likely beneficial during COVID-19 infection for hypertensive and normotensive patients.
Literature
1.
go back to reference Cao Y, Li L, Feng Z, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov. 2020;6:11.CrossRef Cao Y, Li L, Feng Z, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov. 2020;6:11.CrossRef
3.
go back to reference Chen J, Jiang Q, Xia X, Liu K, Yu Z, Tao W, Gong W, Han JJ. Individual variation of the SARS-CoV2 receptor ACE2 gene expression and regulation; 2020. p. 2020030191. Chen J, Jiang Q, Xia X, Liu K, Yu Z, Tao W, Gong W, Han JJ. Individual variation of the SARS-CoV2 receptor ACE2 gene expression and regulation; 2020. p. 2020030191.
6.
go back to reference Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, Leopoldi A, Garreta E, del Pozo CH, Prosper F, Romero JP, Wirnsberger G, Zhang H, Slutsky AS, Conder R, Montserrat N, Mirazimi A, Penninger JM. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. 2020;181:905–913.e7. https://doi.org/10.1016/j.cell.2020.04.004. Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, Leopoldi A, Garreta E, del Pozo CH, Prosper F, Romero JP, Wirnsberger G, Zhang H, Slutsky AS, Conder R, Montserrat N, Mirazimi A, Penninger JM. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. 2020;181:905–913.e7. https://​doi.​org/​10.​1016/​j.​cell.​2020.​04.​004.
9.
go back to reference Glowacka I, Bertram S, Herzog P, Pfefferle S, Steffen I, Muench MO, Simmons G, Hofmann H, Kuri T, Weber F, Eichler J, Drosten C, Pöhlmann S. Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63. J Virol. 2010;84(2):1198–205. https://doi.org/10.1128/JVI.01248-09 Epub 2009;28.CrossRefPubMed Glowacka I, Bertram S, Herzog P, Pfefferle S, Steffen I, Muench MO, Simmons G, Hofmann H, Kuri T, Weber F, Eichler J, Drosten C, Pöhlmann S. Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63. J Virol. 2010;84(2):1198–205. https://​doi.​org/​10.​1128/​JVI.​01248-09 Epub 2009;28.CrossRefPubMed
11.
go back to reference Gonzalez AA, Gallardo M, Cespedes C, Vio CP. Potassium intakes prevents the induction of the Renin Angiotensin System and increases medullary ACE1 and COX-2 in the kidneys of Angiotensin II dependent hypertensive rats. Front Pharmacol. 2019;10:1212.CrossRef Gonzalez AA, Gallardo M, Cespedes C, Vio CP. Potassium intakes prevents the induction of the Renin Angiotensin System and increases medullary ACE1 and COX-2 in the kidneys of Angiotensin II dependent hypertensive rats. Front Pharmacol. 2019;10:1212.CrossRef
14.
go back to reference Xu J, Yang J, Chen J, Luo Q, Zhang Q, Zhang H. Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol Med Rep. 2017;16(5):7432–8.CrossRef Xu J, Yang J, Chen J, Luo Q, Zhang Q, Zhang H. Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol Med Rep. 2017;16(5):7432–8.CrossRef
15.
go back to reference Clarke NE, Belyaev ND, Lambert DW. Turner AJ epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress. Clin Sci (Lond). 2014;126(7):507–16.CrossRef Clarke NE, Belyaev ND, Lambert DW. Turner AJ epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress. Clin Sci (Lond). 2014;126(7):507–16.CrossRef
16.
go back to reference Patel VB, Zhong JC, Grant MB, Oudit GY. Role of the ACE2/Angiotensin 1–7 axis of the renin-angiotensin system in heart failure. Circ Res. 2016;118(8):1313–26.CrossRef Patel VB, Zhong JC, Grant MB, Oudit GY. Role of the ACE2/Angiotensin 1–7 axis of the renin-angiotensin system in heart failure. Circ Res. 2016;118(8):1313–26.CrossRef
17.
go back to reference Yu W, Qin J, Chen C, Fu Y, Wang W. Moderate calorie restriction attenuates age-associated alterations and improves cardiac function by increasing SIRT1 and SIRT3 expression. Mol Med Rep. 2018;18(4):4087–94.PubMed Yu W, Qin J, Chen C, Fu Y, Wang W. Moderate calorie restriction attenuates age-associated alterations and improves cardiac function by increasing SIRT1 and SIRT3 expression. Mol Med Rep. 2018;18(4):4087–94.PubMed
18.
go back to reference Kim EN, Kim MY, Lim JH, Kim Y, Shin SJ, Park CW, Kim YS, Chang YS, Yoon HE, Choi BS. The protective effect of resveratrol on vascular aging by modulation of the renin-angiotensin system. Atherosclerosis. 2018;270:123–31.CrossRef Kim EN, Kim MY, Lim JH, Kim Y, Shin SJ, Park CW, Kim YS, Chang YS, Yoon HE, Choi BS. The protective effect of resveratrol on vascular aging by modulation of the renin-angiotensin system. Atherosclerosis. 2018;270:123–31.CrossRef
19.
go back to reference Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005;280(17):17187–95.CrossRef Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005;280(17):17187–95.CrossRef
20.
go back to reference Aşcı H, Saygın M, Yeşilot Ş, Topsakal Ş, Cankara FN, Özmen Ö, Savran M. Protective effects of aspirin and vitamin C against corn syrup consumption-induced cardiac damage through sirtuin-1 and HIF-1α pathway. Anatol J Cardiol. 2016;16(9):648–54.PubMed Aşcı H, Saygın M, Yeşilot Ş, Topsakal Ş, Cankara FN, Özmen Ö, Savran M. Protective effects of aspirin and vitamin C against corn syrup consumption-induced cardiac damage through sirtuin-1 and HIF-1α pathway. Anatol J Cardiol. 2016;16(9):648–54.PubMed
21.
go back to reference Qi MZ, Yao Y, Xie RL, Sun SL, Sun WW, Wang JL, Chen Y, Zhao B, Chen EZ, Mao EQ. Intravenous Vitamin C attenuates hemorrhagic shock-related renal injury through the induction of SIRT1 in rats. Biochem Biophys Res Commun. 2018;501(2):358–64.CrossRef Qi MZ, Yao Y, Xie RL, Sun SL, Sun WW, Wang JL, Chen Y, Zhao B, Chen EZ, Mao EQ. Intravenous Vitamin C attenuates hemorrhagic shock-related renal injury through the induction of SIRT1 in rats. Biochem Biophys Res Commun. 2018;501(2):358–64.CrossRef
22.
go back to reference Cuyàs E, Verdura S, Llorach-Parés L, Fernández-Arroyo S, Joven J, Martin-Castillo B, Bosch-Barrera J, Brunet J, Nonell-Canals A, Sanchez-Martinez M, Menendez JA. Metformin is a direct SIRT1-activating compound: computational modeling and experimental validation. Front Endocrinol. 2018;9:657.CrossRef Cuyàs E, Verdura S, Llorach-Parés L, Fernández-Arroyo S, Joven J, Martin-Castillo B, Bosch-Barrera J, Brunet J, Nonell-Canals A, Sanchez-Martinez M, Menendez JA. Metformin is a direct SIRT1-activating compound: computational modeling and experimental validation. Front Endocrinol. 2018;9:657.CrossRef
23.
go back to reference Hong G, Zheng D, Zhang L, Ni R, Wang G, Fan GC, Lu Z, Peng T. Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis. Free Radic Biol Med. 2018;123:125–37.CrossRef Hong G, Zheng D, Zhang L, Ni R, Wang G, Fan GC, Lu Z, Peng T. Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis. Free Radic Biol Med. 2018;123:125–37.CrossRef
Metadata
Title
The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms
Author
Craig Steven McLachlan
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Clinical Hypertension / Issue 1/2020
Electronic ISSN: 2056-5909
DOI
https://doi.org/10.1186/s40885-020-00147-x

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