TY - JOUR
T1 - Effects of sars‐cov‐2 on cardiovascular system
T2 - The dual role of angiotensin‐converting enzyme 2 (ace2) as the virus receptor and homeostasis regulator‐review
AU - Aleksova, Aneta
AU - Gagno, Giulia
AU - Sinagra, Gianfranco
AU - Beltrami, Antonio Paolo
AU - Janjusevic, Milijana
AU - Ippolito, Giuseppe
AU - Zumla, Alimuddin
AU - Fluca, Alessandra Lucia
AU - Ferro, Federico
N1 - Funding Information:
Zumla and Ippolito, are co?PI?s of the European and Developing Countries Clinical Trials Partnership the EU Horizon 2020 Framework Program, projects a) Pan?African Net-work on Emerging and Re?Emerging Infections (Available online: https://www.pandora?id.net/ (ac-cessed on April 2021)). Sir Zumla is in receipt of a UK?National Institutes of Health Research Senior Investigator award and is a 2020 Mahathir Science Award Laureate. The National Institute for Infectious Diseases Lazzaro Spallanzani?IRCCS, Rome, Italy has been funded by the Italian Ministry of Health (Ricerca Corrente line 1, COVID?2020?12371735 and COVID?2020? 12371817).
Funding Information:
Investigator award and is a 2020 Mahathir Science Award Laureate. The National Institute for In‐ fectious Diseases Lazzaro Spallanzani‐IRCCS, Rome, Italy has been funded by the Italian Ministry of Health (Ricerca Corrente line 1, COVID‐2020‐12371735 and COVID‐2020‐ 12371817).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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 homeo-static 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 comor-bidities. 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 Angio-tensin 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.
AB - 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 homeo-static 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 comor-bidities. 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 Angio-tensin 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.
KW - ACE2
KW - ADAM17
KW - Cardiovascular system
KW - COVID‐19
KW - Pandemic
KW - RAS
KW - SARS‐ CoV‐2
KW - TMPRSS2
KW - Vaccines
UR - http://www.scopus.com/inward/record.url?scp=85104653646&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85104653646&partnerID=8YFLogxK
U2 - 10.3390/ijms22094526
DO - 10.3390/ijms22094526
M3 - Review article
C2 - 33926110
AN - SCOPUS:85104653646
VL - 22
SP - 1
EP - 14
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 9
M1 - 4526
ER -