Endotyping COPD: hypoxia-inducible factor-2 as a molecular "switch" between the vascular and airway phenotypes?

Myronenko, Oleh ORCID: 0000-0001-5221-7218, Foris, Vasile, Crnkovic, Slaven, Olschewski, Andrea ORCID: 0000-0002-8189-3634, Rocha, Sonia, Nicolls, Mark R ORCID: 0000-0001-9473-7422 and Olschewski, Horst (2023) Endotyping COPD: hypoxia-inducible factor-2 as a molecular "switch" between the vascular and airway phenotypes? European respiratory review : an official journal of the European Respiratory Society, 32 (167). 220173-.

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Official URL: http://dx.doi.org/10.1183/16000617.0173-2022

Abstract

COPD is a heterogeneous disease with multiple clinical phenotypes. COPD endotypes can be determined by different expressions of hypoxia-inducible factors (HIFs), which, in combination with individual susceptibility and environmental factors, may cause predominant airway or vascular changes in the lung. The pulmonary vascular phenotype is relatively rare among COPD patients and characterised by out-of-proportion pulmonary hypertension (PH) and low diffusing capacity of the lung for carbon monoxide, but only mild-to-moderate airway obstruction. Its histologic feature, severe remodelling of the small pulmonary arteries, can be mediated by HIF-2 overexpression in experimental PH models. HIF-2 is not only involved in the vascular remodelling but also in the parenchyma destruction. Endothelial cells from human emphysema lungs express reduced HIF-2α levels, and the deletion of pulmonary endothelial <i>Hif-2</i>α leads to emphysema in mice. This means that both upregulation and downregulation of HIF-2 have adverse effects and that HIF-2 may represent a molecular "switch" between the development of the vascular and airway phenotypes in COPD. The mechanisms of HIF-2 dysregulation in the lung are only partly understood. HIF-2 levels may be controlled by NAD(P)H oxidases <i>via</i> iron- and redox-dependent mechanisms. A better understanding of these mechanisms may lead to the development of new therapeutic targets.

Item Type:	Article
Uncontrolled Keywords:	Endothelial Cells, Animals, Humans, Mice, Hypertension, Pulmonary, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Emphysema, Basic Helix-Loop-Helix Transcription Factors, Hypoxia
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	29 Sep 2023 09:44
Last Modified:	29 Sep 2023 09:44
DOI:	10.1183/16000617.0173-2022
Open Access URL:	https://err.ersjournals.com/content/32/167/220173
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3173199