The Role of Sex in the Pathophysiology of Pulmonary Hypertension

  • Craig K. Docherty
  • Katie Yates Harvey
  • Kirsty M. Mair
  • Sinead Griffin
  • Nina Denver
  • Margaret R. MacLeanEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1065)


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.


Pulmonary arterial hypertension Vascular remodelling Sex hormones Estrogen Estrogen metabolites Serotonin 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Craig K. Docherty
    • 1
  • Katie Yates Harvey
    • 1
  • Kirsty M. Mair
    • 1
  • Sinead Griffin
    • 1
  • Nina Denver
    • 1
  • Margaret R. MacLean
    • 1
    Email author
  1. 1.Research Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of GlasgowGlasgowUK

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