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Volchkova E.V.
Saint Petersburg State Pediatric Medical University
Kuzubova N.A.
Pavlov First Saint Petersburg State Medical University
Aleksandrovich Yu.S.
Children’s Scientific Clinical Center for Infectious Diseases
Lebedeva E.S.
Pavlov First Saint Petersburg State Medical University
HIF-1a in immune pathogenesis of SARS-CoV-2-pneumonia
Journal: Russian Journal of Anesthesiology and Reanimatology. 2022;(5): 71‑78
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To cite this article:
Volchkova EV, Kuzubova NA, Aleksandrovich YuS, Lebedeva ES. HIF-1a in immune pathogenesis of SARS-CoV-2-pneumonia. Russian Journal of Anesthesiology and Reanimatology.
2022;(5):71‑78. (In Russ.)
https://doi.org/10.17116/anaesthesiology202205171
The review is devoted to cellular and molecular mechanisms of the course and progression of new coronavirus disease, in particular, the role of hypoxia and hypoxia-induced factor 1α (HIF-1α). Literature searching was performed in the PubMed, Medline and Web of Science databases for the period 2019—2022. Hypoxia is a direct consequence of lung damage due to COVID-19 infection. In the areas of SARS-CoV-2-induced damage, focal inflammation occurs, and tissue microenvironment becomes hypoxic («inflammatory hypoxia»). Possible causes of «silent», «happy» or «apathetic» hypoxia in patients with COVID-19 and no symptoms of respiratory discomfort are discussed. HIF-1α activated by hypoxia is generally considered to be the main regulator of cellular response to oxygen deficiency. There is no consensus regarding the role of its activation in pathogenesis of COVID-19. As a transcriptional factor, HIF-1α can reduce penetration of SARS-CoV-2 via proteins controlling its entry into cells. This protein also reduces angiotensin-converting enzyme 2 receptor (ACE2) and serine protease expression, as well as increases expression of ADAM17 enzyme, which cleaves ACE2 from surface membrane of alveolocyte. The reverse side of HIF-1α activation may be fulminant cytokine storm as a result of expression of immune cells releasing pro-inflammatory cytokines. Possible HIF-dependent approaches to the treatment and prevention of COVID-19 are considered. These approaches are aimed at either suppressing HIF-1α activity using HIF-1α suppressor drugs or activating and stabilizing HIF-1α using HIF prolyl hydroxylase inhibitors.
Keywords:
Authors:
Volchkova E.V.
Saint Petersburg State Pediatric Medical University
Kuzubova N.A.
Pavlov First Saint Petersburg State Medical University
Aleksandrovich Yu.S.
Children’s Scientific Clinical Center for Infectious Diseases
Lebedeva E.S.
Pavlov First Saint Petersburg State Medical University
Received:
30.06.2022
Accepted:
18.07.2022
List of references:
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