Hypoxia-induced pulmonary hypertension—Utilizing experiments of nature

Max Gassmann, Andrew Cowburn, Hong Gu, Jia Li, Marisela Rodriguez, Aleksandra Babicheva, Pritesh P. Jain, Mingmei Xiong, Norina N. Gassmann, Jason X.J. Yuan, Martin R. Wilkins, Lan Zhao

Research output: Contribution to journalReview articlepeer-review

Abstract

An increase in pulmonary artery pressure is a common observation in adult mammals exposed to global alveolar hypoxia. It is considered a maladaptive response that places an increased workload on the right ventricle. The mechanisms initiating and maintaining the elevated pressure are of considerable interest in understanding pulmonary vascular homeostasis. There is an expectation that identifying the key molecules in the integrated vascular response to hypoxia will inform potential drug targets. One strategy is to take advantage of experiments of nature, specifically, to understand the genetic basis for the inter-individual variation in the pulmonary vascular response to acute and chronic hypoxia. To date, detailed phenotyping of highlanders has focused on haematocrit and oxygen saturation rather than cardiovascular phenotypes. This review explores what we can learn from those studies with respect to the pulmonary circulation.

Original languageEnglish (US)
JournalBritish Journal of Pharmacology
DOIs
StateAccepted/In press - 2020

Keywords

  • genetics
  • high-altitude
  • hypoxia-inducible factor
  • hypoxiainducible factor prolyl hydroxylase 2
  • oxygen sensing
  • pulmonary vasoconstriction
  • vascular remodelling

ASJC Scopus subject areas

  • Pharmacology

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