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October 21, 2020Current Drug Targets

Downregulation of membrane-bound ACE2 by SARS-CoV-2 leads to increased Angiotensin II levels, resulting in increased inflammation, thrombosis, and angiogenesis.

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Why the study?

To describe the intimate connections between renin-angiotensin system components, the immune system, and COVID-19 pathophysiology.

Design

Non-systematic review article

Authors

CVCristina Cerqueira VieiraLNLucas NeryLMLudimila de Barcelos Ubaldo Martins

Discussion

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Overview

May inform RAS-modulator strategies in COVID-19; extends prior coronavirus data to SARS-CoV-2 lung injury.

Key Points

  • To synthesize evidence on the molecular mechanisms connecting renin-angiotensin system disruption, immune dysregulation, and COVID-19 pathophysiology.
  • Non-systematic literature review evaluating published evidence on SARS-CoV-2 infection mechanisms and renin-angiotensin system alterations.
  • Membrane-bound ACE2 is depleted during SARS-CoV-2 infection through virus-induced shedding, viral endocytosis, and immune-mediated interferon inhibition.
  • Loss of functional ACE2 suppresses protective Angiotensin-(1-7) generation and elevates Angiotensin II levels, driving AT1 receptor overactivation that promotes systemic inflammation, thrombosis, and angiogenesis.

Structured PICO

P
Population
Patients with COVID-19

SARS-CoV-2 infection downregulates membrane-bound ACE2, leading to an imbalance in the renin-angiotensin system that promotes inflammation and thrombosis.

Cite This Study

Vieira et al. (2020) studied this question.

synapsesocial.com/papers/6a720612fe4101aa97e0be2fhttps://doi.org/10.2174/1389450121666201020154033
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Angiotensin-Converting Enzyme 2 Roles in the Pathogenesis of COVID-192020 · 10 citations
  2. 2Dysregulation of the Renin-Angiotensin-Aldosterone System (RAA) in Patients Infected with SARS-CoV-2-Possible Clinical Consequences2021 · 23 citations
  3. 3Regulation of Angiotensin-Converting Enzyme 2: A Potential Target to Prevent COVID-19?2021 · 22 citations
  4. 4The Counter-Regulatory Renin-Angiotensin System: A Surprising Ally in the Field of COVID-192025
  5. 5Linking ACE2 and angiotensin II to pulmonary immunovascular dysregulation in SARS-CoV-2 infection2020 · 29 citations