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Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection

Deepraj Paul, Suresh Mohankumar Orcid Logo, Rhian Thomas Orcid Logo, Chai B. Kheng, Duraiswamy Basavan

Current Drug Targets, Volume: 23, Issue: 4, Pages: 364 - 372

Swansea University Authors: Suresh Mohankumar Orcid Logo, Rhian Thomas Orcid Logo

Abstract

Angiotensin-converting enzyme 2 (ACE2) has been reported as a portal for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, scientific strategies to combat coronavirus disease of 2019 (COVID-19) were targeted to arrest SARS-CoV-2 invasion by blocking ACE2. Whil...

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Published in: Current Drug Targets
ISSN: 1389-4501 1873-5592
Published: Bentham Science Publishers Ltd. 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa58742
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spelling v2 58742 2021-11-22 Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection edce0da45e3933d3460963b966f4c84e 0000-0001-8862-2979 Suresh Mohankumar Suresh Mohankumar true false 10f33f117e548cddfa6758ea130c3407 0000-0002-7286-2764 Rhian Thomas Rhian Thomas true false 2021-11-22 MEDS Angiotensin-converting enzyme 2 (ACE2) has been reported as a portal for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, scientific strategies to combat coronavirus disease of 2019 (COVID-19) were targeted to arrest SARS-CoV-2 invasion by blocking ACE2. While blocking ACE2 appears a beneficial approach to treat COVID-19, clinical concerns have been raised primarily due to the various intrinsic roles of ACE2 in neurological functions. Selective reports indicate that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) upregulate ACE2 levels. ACE2 metabolizes angiotensin II and several peptides, including apelin-13, neurotensin, kinetensin, dynorphin, [des-Arg9] bradykinin, and [Lys-des-Arg9]-bradykinin, which may elicit neuroprotective effects. Since ARBs and ACEIs upregulate ACE2, it may be hypothesized that patients with hypertension receiving ARBs and ACEIs may have higher expression of ACE2 and thus be at a greater risk of severe disease from the SARS-CoV-2 infections. However, recent clinical reports indicate the beneficial role of ARBs/ACEIs in reducing COVID-19 severity. Together, this warrants a further study of the effects of ACE2 blockades in hypertensive patients medicated with ARBs/ACEIs, and their consequential impact on neuronal health. However, the associations between their blockade and any neuroinflammation also warrant further research. This review collates mechanistic insights into the dichotomous roles of ACE2 in SARS-CoV-2 invasion and neurometabolic functions and the possible impact of ACE2 blockade on neuroinflammation. It has been concluded that ACE2 blockade imposes neuroinflammation. [Abstract copyright: Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.] Journal Article Current Drug Targets 23 4 364 372 Bentham Science Publishers Ltd. 1389-4501 1873-5592 neuroinflammation, COVID-19, angiotensin-converting enzyme 2, hypertension, SARS-CoV-2 1 3 2022 2022-03-01 10.2174/1389450122666211103165837 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University 2024-08-05T13:53:04.3040739 2021-11-22T13:21:08.3074541 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Deepraj Paul 1 Suresh Mohankumar 0000-0001-8862-2979 2 Rhian Thomas 0000-0002-7286-2764 3 Chai B. Kheng 4 Duraiswamy Basavan 5 58742__21737__66cb7dbeea094e1b97dea3d6399baffb.pdf 58742.pdf 2021-11-30T15:36:53.8010275 Output 480156 application/pdf Accepted Manuscript true 2022-11-03T00:00:00.0000000 true eng
title Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
spellingShingle Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
Suresh Mohankumar
Rhian Thomas
title_short Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
title_full Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
title_fullStr Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
title_full_unstemmed Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
title_sort Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
author_id_str_mv edce0da45e3933d3460963b966f4c84e
10f33f117e548cddfa6758ea130c3407
author_id_fullname_str_mv edce0da45e3933d3460963b966f4c84e_***_Suresh Mohankumar
10f33f117e548cddfa6758ea130c3407_***_Rhian Thomas
author Suresh Mohankumar
Rhian Thomas
author2 Deepraj Paul
Suresh Mohankumar
Rhian Thomas
Chai B. Kheng
Duraiswamy Basavan
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publishDate 2022
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department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Angiotensin-converting enzyme 2 (ACE2) has been reported as a portal for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, scientific strategies to combat coronavirus disease of 2019 (COVID-19) were targeted to arrest SARS-CoV-2 invasion by blocking ACE2. While blocking ACE2 appears a beneficial approach to treat COVID-19, clinical concerns have been raised primarily due to the various intrinsic roles of ACE2 in neurological functions. Selective reports indicate that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) upregulate ACE2 levels. ACE2 metabolizes angiotensin II and several peptides, including apelin-13, neurotensin, kinetensin, dynorphin, [des-Arg9] bradykinin, and [Lys-des-Arg9]-bradykinin, which may elicit neuroprotective effects. Since ARBs and ACEIs upregulate ACE2, it may be hypothesized that patients with hypertension receiving ARBs and ACEIs may have higher expression of ACE2 and thus be at a greater risk of severe disease from the SARS-CoV-2 infections. However, recent clinical reports indicate the beneficial role of ARBs/ACEIs in reducing COVID-19 severity. Together, this warrants a further study of the effects of ACE2 blockades in hypertensive patients medicated with ARBs/ACEIs, and their consequential impact on neuronal health. However, the associations between their blockade and any neuroinflammation also warrant further research. This review collates mechanistic insights into the dichotomous roles of ACE2 in SARS-CoV-2 invasion and neurometabolic functions and the possible impact of ACE2 blockade on neuroinflammation. It has been concluded that ACE2 blockade imposes neuroinflammation. [Abstract copyright: Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.]
published_date 2022-03-01T13:53:03Z
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