Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review
Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/9/4526 |
| _version_ | 1797536169853976576 |
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| author | Aneta Aleksova Giulia Gagno Gianfranco Sinagra Antonio Paolo Beltrami Milijana Janjusevic Giuseppe Ippolito Alimuddin Zumla Alessandra Lucia Fluca Federico Ferro |
| author_facet | Aneta Aleksova Giulia Gagno Gianfranco Sinagra Antonio Paolo Beltrami Milijana Janjusevic Giuseppe Ippolito Alimuddin Zumla Alessandra Lucia Fluca Federico Ferro |
| author_sort | Aneta Aleksova |
| collection | DOAJ |
| description | Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in testes and gastrointestinal tract. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein. However, ACE2 is not only a SARS-CoV-2 receptor, but it has also an important homeostatic function regulating renin-angiotensin system (RAS), which is pivotal for both the cardiovascular and immune systems. Therefore, ACE2 is the key link between SARS-CoV-2 infection, cardiovascular diseases (CVDs) and immune response. Susceptibility to SARS-CoV-2 seems to be tightly associated with ACE2 availability, which in turn is determined by genetics, age, gender and comorbidities. Severe COVID-19 is due to an uncontrolled and excessive immune response, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. In spite of a lower ACE2 expression on cells surface, patients with CVDs have a higher COVID-19 mortality rate, which is likely driven by the imbalance between ADAM metallopeptidase domain 17 (ADAM17) protein (which is required for cleavage of ACE-2 ectodomain resulting in increased ACE2 shedding), and TMPRSS2 (which is required for spike glycoprotein priming). To date, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) treatment interruption in patients with chronic comorbidities appears unjustified. The rollout of COVID-19 vaccines provides opportunities to study the effects of different COVID-19 vaccines on ACE2 in patients on treatment with ACEi/ARB. |
| first_indexed | 2024-03-10T11:56:53Z |
| format | Article |
| id | doaj.art-441b893a9f234903b175b9cdf48e5b97 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:56:53Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-441b893a9f234903b175b9cdf48e5b972023-11-21T17:16:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01229452610.3390/ijms22094526Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-ReviewAneta Aleksova0Giulia Gagno1Gianfranco Sinagra2Antonio Paolo Beltrami3Milijana Janjusevic4Giuseppe Ippolito5Alimuddin Zumla6Alessandra Lucia Fluca7Federico Ferro8Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, ItalyCardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, ItalyCardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, ItalyDepartment of Medicine (DAME), University of Udine, 33100 Udine, ItalyCardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, ItalyNational Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00135 Rome, ItalyDepartment of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London NW3 2PF, UKCardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, ItalyCardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, ItalyAngiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in testes and gastrointestinal tract. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein. However, ACE2 is not only a SARS-CoV-2 receptor, but it has also an important homeostatic function regulating renin-angiotensin system (RAS), which is pivotal for both the cardiovascular and immune systems. Therefore, ACE2 is the key link between SARS-CoV-2 infection, cardiovascular diseases (CVDs) and immune response. Susceptibility to SARS-CoV-2 seems to be tightly associated with ACE2 availability, which in turn is determined by genetics, age, gender and comorbidities. Severe COVID-19 is due to an uncontrolled and excessive immune response, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. In spite of a lower ACE2 expression on cells surface, patients with CVDs have a higher COVID-19 mortality rate, which is likely driven by the imbalance between ADAM metallopeptidase domain 17 (ADAM17) protein (which is required for cleavage of ACE-2 ectodomain resulting in increased ACE2 shedding), and TMPRSS2 (which is required for spike glycoprotein priming). To date, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) treatment interruption in patients with chronic comorbidities appears unjustified. The rollout of COVID-19 vaccines provides opportunities to study the effects of different COVID-19 vaccines on ACE2 in patients on treatment with ACEi/ARB.https://www.mdpi.com/1422-0067/22/9/4526cardiovascular systemACE2RASCOVID-19SARS- CoV-2TMPRSS2 |
| spellingShingle | Aneta Aleksova Giulia Gagno Gianfranco Sinagra Antonio Paolo Beltrami Milijana Janjusevic Giuseppe Ippolito Alimuddin Zumla Alessandra Lucia Fluca Federico Ferro Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review International Journal of Molecular Sciences cardiovascular system ACE2 RAS COVID-19 SARS- CoV-2 TMPRSS2 |
| title | Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review |
| title_full | Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review |
| title_fullStr | Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review |
| title_full_unstemmed | Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review |
| title_short | Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review |
| title_sort | effects of sars cov 2 on cardiovascular system the dual role of angiotensin converting enzyme 2 ace2 as the virus receptor and homeostasis regulator review |
| topic | cardiovascular system ACE2 RAS COVID-19 SARS- CoV-2 TMPRSS2 |
| url | https://www.mdpi.com/1422-0067/22/9/4526 |
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