Therapeutic targeting of hypoxia inducible factor in acute respiratory distress syndrome

Thu T Tran; Holger K Eltzschig; Xiaoyi Yuan

doi:10.1113/JP284599

Therapeutic targeting of hypoxia inducible factor in acute respiratory distress syndrome

J Physiol. 2023 Nov 30:10.1113/JP284599. doi: 10.1113/JP284599. Online ahead of print.

Authors

Thu T Tran¹, Holger K Eltzschig², Xiaoyi Yuan²

Affiliations

¹ Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
² Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

PMID: 38031820
PMCID: PMC11136894 (available on 2025-05-30)
DOI: 10.1113/JP284599

Abstract

Acute respiratory distress syndrome (ARDS) is characterized by bilateral chest infiltration and acute hypoxic respiratory failure. ARDS carries significant morbidity and mortality despite advancements in medical management, calling for the development of novel therapeutic targets. Hypoxia-inducible factor (HIF) is a heterodimeric protein involved in various essential pathways, including metabolic reprogramming, immune modulation, angiogenesis and cell cycle regulation. HIF is routinely degraded in homeostasis conditions via the prolyl hydroxylase domain/von Hippel-Lindau protein pathway. However, HIF is stabilized in ARDS via various mechanisms (oxygen-dependent and independent) as an endogenous protective pathway and plays multifaceted roles in different cell populations. This review focuses on the functional role of HIF and its target genes during ARDS, as well as how HIF has evolved as a therapeutic target in current medical management.

Keywords: ARDS; HIF; hypoxia signalling; target genes.

Abstract

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