The role of sex in the pathophysiology of pulmonary hypertension

Docherty, C. K., Harvey, K. Y., Mair, K. M., Griffin, S., Denver, N. and MacLean, M. R. (2018) The role of sex in the pathophysiology of pulmonary hypertension. In: Kerkhof, P. L.M. and Miller, V. M. (eds.) Sex-Specific Analysis of Cardiovascular Function. Series: Advances in experimental medicine and biology (1065). Springer: Cham, pp. 511-528. ISBN 9783319779317 (doi: 10.1007/978-3-319-77932-4_31)

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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.

Item Type:Book Sections
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLean, Professor Margaret and Harvey, Dr Katie and Griffin, Sinead and Docherty, Dr Craig and Denver, Nina and Mair, Dr Kirsty
Authors: Docherty, C. K., Harvey, K. Y., Mair, K. M., Griffin, S., Denver, N., and MacLean, M. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Advances in experimental medicine and biology
Publisher:Springer
ISBN:9783319779317
Published Online:27 July 2018
Copyright Holders:Copyright © 2018 Springer International Publishing AG, part of Springer Nature
First Published:First published in Sex-Specific Analysis of Cardiovascular Function: 511-528
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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