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. MacLean

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)

Abstract

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.

LanguageEnglish
Title of host publicationSex-Specific Analysis of Cardiovascular Function
EditorsPeter L. M. Kerkhof, Virginia M. Miller
Place of PublicationCham, Switzerland
PublisherSpringer
Chapter31
Pages511-528
Number of pages18
ISBN (Print)9783319779317, 9783319779324
DOIs
Publication statusPublished - 4 Aug 2018

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1065
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Fingerprint

Pulmonary Hypertension
Estrogens
Type II Bone Morphogenetic Protein Receptors
Cell proliferation
Metabolites
Metabolism
Pulmonary Artery
Hydroxyestrones
Blood Vessels
Cell Proliferation
Gonadal Steroid Hormones
Mutation
Pulmonary Circulation
Penetrance
Muscle
Serotonin
Vascular Resistance
Smooth Muscle Myocytes
Up-Regulation
Heart Failure

Keywords

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

Cite this

Docherty, C. K., Harvey, K. Y., Mair, K. M., Griffin, S., Denver, N., & MacLean, M. R. (2018). The role of sex in the pathophysiology of pulmonary hypertension. In P. L. M. Kerkhof, & V. M. Miller (Eds.), Sex-Specific Analysis of Cardiovascular Function (pp. 511-528). (Advances in Experimental Medicine and Biology; Vol. 1065). Cham, Switzerland: Springer. https://doi.org/10.1007/978-3-319-77932-4_31
Docherty, Craig K. ; Harvey, Katie Yates ; Mair, Kirsty M. ; Griffin, Sinead ; Denver, Nina ; MacLean, Margaret R. / The role of sex in the pathophysiology of pulmonary hypertension. Sex-Specific Analysis of Cardiovascular Function. editor / Peter L. M. Kerkhof ; Virginia M. Miller. Cham, Switzerland : Springer, 2018. pp. 511-528 (Advances in Experimental Medicine and Biology).
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Docherty, CK, Harvey, KY, Mair, KM, Griffin, S, Denver, N & MacLean, MR 2018, The role of sex in the pathophysiology of pulmonary hypertension. in PLM Kerkhof & VM Miller (eds), Sex-Specific Analysis of Cardiovascular Function. Advances in Experimental Medicine and Biology, vol. 1065, Springer, Cham, Switzerland, pp. 511-528. https://doi.org/10.1007/978-3-319-77932-4_31

The role of sex in the pathophysiology of pulmonary hypertension. / Docherty, Craig K.; Harvey, Katie Yates; Mair, Kirsty M.; Griffin, Sinead; Denver, Nina; MacLean, Margaret R.

Sex-Specific Analysis of Cardiovascular Function. ed. / Peter L. M. Kerkhof; Virginia M. Miller. Cham, Switzerland : Springer, 2018. p. 511-528 (Advances in Experimental Medicine and Biology; Vol. 1065).

Research output: Chapter in Book/Report/Conference proceedingChapter

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T1 - The role of sex in the pathophysiology of pulmonary hypertension

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AU - Harvey, Katie Yates

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N2 - 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.

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Docherty CK, Harvey KY, Mair KM, Griffin S, Denver N, MacLean MR. The role of sex in the pathophysiology of pulmonary hypertension. In Kerkhof PLM, Miller VM, editors, Sex-Specific Analysis of Cardiovascular Function. Cham, Switzerland: Springer. 2018. p. 511-528. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-3-319-77932-4_31