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Front. Med. | doi: 10.3389/fmed.2019.00093

Thin Air, Thick Vessels: Historical and Current Perspectives on Hypoxic Pulmonary Hypertension

 Jason Young1, 2, David R. Williams2 and  A. A. Roger Thompson2, 3*
  • 1Edinburgh Medical School, University of Edinburgh, United Kingdom
  • 2Apex (Altitude Physiology Expeditions), United Kingdom
  • 3Infection, Immunity and Cardiovascular Disease, University of Sheffield, United Kingdom

The association between pulmonary hypertension (PH) and hypoxia is well-established, with two key mechanistic processes, hypoxic pulmonary vasoconstriction and hypoxia-induced vascular remodelling, driving changes in pulmonary arterial pressure. In contrast to other forms of pulmonary hypertension, the vascular changes induced by hypoxia are reversible, both in humans returning to sea-level from high altitude and in animal models. This raises the intriguing possibility that molecular drivers of hypoxic processes could be targeted to modify pulmonary vascular remodelling in other contexts. In this review, we outline the history of research into PH and hypoxia, before discussing recent advances in our understanding of this relationship at the molecular level, focussing on the role of the oxygen-sensing transcription factors, hypoxia inducible factors (HIFs). Emerging links between HIF and vascular remodelling highlight the potential utility of inhibiting this pathway in pulmonary hypertension and raise possible risks of activating this pathway using HIF-stabilising medications.

Keywords: hypoxia, pulmonary hypertension, altitude, vascular remodeling, Hypoxic Pulmonary Vasoconstriction (HPV)

Received: 10 Jan 2019; Accepted: 16 Apr 2019.

Edited by:

Claudio Sartori, Université de Lausanne, Switzerland

Reviewed by:

Erik R. Swenson, University of Washington, United States
Robert Naeije, Free University of Brussels, Belgium  

Copyright: © 2019 Young, Williams and Thompson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. A. A. Roger Thompson, University of Sheffield, Infection, Immunity and Cardiovascular Disease, Sheffield, United Kingdom, R.Thompson@sheffield.ac.uk