The role of sex in the pathophysiology of pulmonary hypertension

Craig Kenneth Docherty, Katie Harvey, Kirsty Mair, Sinead Griffin, Nina Denver, Margaret MacLean

Research output: Chapter in Book/Report/Conference proceedingChapter

27 Citations (Scopus)


Pulmonary arterial hypertension (PAH) is a progressive disease characterised by increased pulmonary vascular resistance and pulmonary artery remodelling as result of increased vascular tone and vascular cell proliferation, respectively. Eventually, this leads to right heart failure. Heritable PAH is caused by a mutation in the bone morphogenetic protein receptor-II (BMPR-II). Female susceptibility to PAH has been known for some time, and most recent figures show a female-to-male ratio of 4:1. Variations in the female sex hormone estrogen and estrogen metabolism modify FPAH risk, and penetrance of the disease in BMPR-II mutation carriers is increased in females. Several lines of evidence point towards estrogen being pathogenic in the pulmonary circulation, and thus increasing the risk of females developing PAH. Recent studies have also suggested that estrogen metabolism may be crucial in the development and progression of PAH with studies indicating that downstream metabolites such as 16α-hydroxyestrone are upregulated in several forms of experimental pulmonary hypertension (PH) and can cause pulmonary artery smooth muscle cell proliferation and subsequent vascular remodelling. Conversely, other estrogen metabolites such as 2-methoxyestradiol have been shown to be protective in the context of PAH. Estrogen may also upregulate the signalling pathways of other key mediators of PAH such as serotonin.

Original languageEnglish
Title of host publicationSex-Specific Analysis of Cardiovascular Function
EditorsPeter L. M. Kerkhof, Virginia M. Miller
Place of PublicationCham, Switzerland
Number of pages18
ISBN (Print)9783319779317, 9783319779324
Publication statusPublished - 4 Aug 2018

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


  • estrogen
  • estrogen metabolites
  • pulmonary arterial hypertension
  • serotonin
  • sex hormones
  • vascular remodelling


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