Hypoxia-induced pulmonary hypertension – utilising experiments of nature


Gassmann M, Cowburn A, Gu H, Li J, Rodriguez M, Babicheva A, Jain PP, Xiong M, Gassmann NN, Yuan JX, Wilkins MR, Zhao L.Br J Pharmacol. 2020 May 28. doi: 10.1111/bph.15144. Online ahead of print.PMID: 32464698 Review.



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 to 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 that cardiovascular phenotypes. This review explores what we can learn from those studies with respect to the pulmonary circulation.