ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System
Angiotensin converting enzyme 2 (ACE2) is the recognized host cell receptor responsible for mediating infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 bound to tissue facilitates infectivity of SARS-CoV-2; thus, one could argue that decreasing ACE2 tissue expression wo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/7/2096 |
| _version_ | 1797563351175266304 |
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| author | Veronique Michaud Malavika Deodhar Meghan Arwood Sweilem B Al Rihani Pamela Dow Jacques Turgeon |
| author_facet | Veronique Michaud Malavika Deodhar Meghan Arwood Sweilem B Al Rihani Pamela Dow Jacques Turgeon |
| author_sort | Veronique Michaud |
| collection | DOAJ |
| description | Angiotensin converting enzyme 2 (ACE2) is the recognized host cell receptor responsible for mediating infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 bound to tissue facilitates infectivity of SARS-CoV-2; thus, one could argue that decreasing ACE2 tissue expression would be beneficial. However, ACE2 catalytic activity towards angiotensin I (Ang I) and II (Ang II) mitigates deleterious effects associated with activation of the renin-angiotensin-aldosterone system (RAAS) on several organs, including a pro-inflammatory status. At the tissue level, SARS-CoV-2 (a) binds to ACE2, leading to its internalization, and (b) favors ACE2 cleavage to form soluble ACE2: these actions result in decreased ACE2 tissue levels. Preserving tissue ACE2 activity while preventing ACE2 shredding is expected to circumvent unrestrained inflammatory response. Concerns have been raised around RAAS modulators and their effects on ACE2 expression or catalytic activity. Various cellular and animal models report conflicting results in various tissues. However, recent data from observational and meta-analysis studies in SARS-CoV-2-infected patients have concluded that RAAS modulators do not increase plasma ACE2 levels or susceptibility to infection and are not associated with more severe diseases. This review presents our current but evolving knowledge of the complex interplay between SARS-CoV-2 infection, ACE2 levels, modulators of RAAS activity and the effects of RAAS modulators on ACE2 expression. |
| first_indexed | 2024-03-10T18:41:23Z |
| format | Article |
| id | doaj.art-414b141d48a5443298459a9daddcea5e |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T18:41:23Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-414b141d48a5443298459a9daddcea5e2023-11-20T05:47:03ZengMDPI AGJournal of Clinical Medicine2077-03832020-07-0197209610.3390/jcm9072096ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS SystemVeronique Michaud0Malavika Deodhar1Meghan Arwood2Sweilem B Al Rihani3Pamela Dow4Jacques Turgeon5Tabula Rasa HealthCare Precision Pharmacotherapy Research & Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare Precision Pharmacotherapy Research & Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare Precision Pharmacotherapy Research & Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare Precision Pharmacotherapy Research & Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare Precision Pharmacotherapy Research & Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare Precision Pharmacotherapy Research & Development Institute, Orlando, FL 32827, USAAngiotensin converting enzyme 2 (ACE2) is the recognized host cell receptor responsible for mediating infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 bound to tissue facilitates infectivity of SARS-CoV-2; thus, one could argue that decreasing ACE2 tissue expression would be beneficial. However, ACE2 catalytic activity towards angiotensin I (Ang I) and II (Ang II) mitigates deleterious effects associated with activation of the renin-angiotensin-aldosterone system (RAAS) on several organs, including a pro-inflammatory status. At the tissue level, SARS-CoV-2 (a) binds to ACE2, leading to its internalization, and (b) favors ACE2 cleavage to form soluble ACE2: these actions result in decreased ACE2 tissue levels. Preserving tissue ACE2 activity while preventing ACE2 shredding is expected to circumvent unrestrained inflammatory response. Concerns have been raised around RAAS modulators and their effects on ACE2 expression or catalytic activity. Various cellular and animal models report conflicting results in various tissues. However, recent data from observational and meta-analysis studies in SARS-CoV-2-infected patients have concluded that RAAS modulators do not increase plasma ACE2 levels or susceptibility to infection and are not associated with more severe diseases. This review presents our current but evolving knowledge of the complex interplay between SARS-CoV-2 infection, ACE2 levels, modulators of RAAS activity and the effects of RAAS modulators on ACE2 expression.https://www.mdpi.com/2077-0383/9/7/2096ACE2SARS-CoV-2renin-angiotensin-aldosterone systemangiotensin II converting enzyme inhibitorsangiotensin II type 1 receptor blockerspneumonia |
| spellingShingle | Veronique Michaud Malavika Deodhar Meghan Arwood Sweilem B Al Rihani Pamela Dow Jacques Turgeon ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System Journal of Clinical Medicine ACE2 SARS-CoV-2 renin-angiotensin-aldosterone system angiotensin II converting enzyme inhibitors angiotensin II type 1 receptor blockers pneumonia |
| title | ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System |
| title_full | ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System |
| title_fullStr | ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System |
| title_full_unstemmed | ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System |
| title_short | ACE2 as a Therapeutic Target for COVID-19; Its Role in Infectious Processes and Regulation by Modulators of the RAAS System |
| title_sort | ace2 as a therapeutic target for covid 19 its role in infectious processes and regulation by modulators of the raas system |
| topic | ACE2 SARS-CoV-2 renin-angiotensin-aldosterone system angiotensin II converting enzyme inhibitors angiotensin II type 1 receptor blockers pneumonia |
| url | https://www.mdpi.com/2077-0383/9/7/2096 |
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