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Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity

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journal contribution
posted on 15.03.2022, 17:08 authored by Maryam Eskandari Mehrabadi, Roohullah Hemmati, Amin Tashakor, Ahmad Homaei, Masoumeh Yousefzadeh, Karim Hemati, Saman Hosseinkhani
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of COVID-19, is reported to increase the rate of mortality worldwide. COVID-19 is associated with acute respiratory symptoms as well as blood coagulation in the vessels (thrombosis), heart attack and stroke. Given the requirement of angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 entry into host cells, here we discuss how the downregulation of ACE2 in the COVID-19 patients and virus-induced shift in ACE2 catalytic equilibrium, change the concentrations of substrates such as angiotensin II, apelin-13, dynorphin-13, and products such as angiotensin (1-7), angiotensin (1-9), apelin-12, dynorphin-12 in the human body. Substrates accumulation ultimately induces inflammation, angiogenesis, thrombosis, neuronal and tissue damage while diminished products lead to the loss of the anti-inflammatory, anti-thrombotic and anti-angiogenic responses. In this review, we focus on the viral-induced imbalance between ACE2 substrates and products which exacerbates the severity of COVID-19. Considering the roadmap, we propose multiple therapeutic strategies aiming to rebalance the products of ACE2 and to ameliorate the symptoms of the disease.

History

Comments

The original article is available at https://www.sciencedirect.com/

Published Citation

Mehrabadi ME, et al. Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity. Biomed Pharmacother. 2021;137:111363.

Publication Date

5 February 2021

PubMed ID

33582450

Department/Unit

  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences

Publisher

Elsevier B.V.

Version

  • Published Version (Version of Record)