Estrogen metabolites in a small cohort of patients with idiopathic pulmonary arterial hypertension

Nina Denver; Natalie Z.M. Homer; Ruth Andrew; Katie Y. Harvey; Nicholas Morrell; Eric D. Austin; Margaret R. MacLean

doi:10.1177/2045894020908783

Estrogen metabolites in a small cohort of patients with idiopathic pulmonary arterial hypertension

Nina Denver, Natalie Z.M. Homer, Ruth Andrew, Katie Y. Harvey, Nicholas Morrell, Eric D. Austin, Margaret R. MacLean

Strathclyde Institute Of Pharmacy And Biomedical Sciences

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Abstract

Increased risk and severity of idiopathic pulmonary arterial hypertension (iPAH) is associated with elevated plasma estradiol (E2) in both men and postmenopausal women, suggesting that E2 is not ovarian-derived. Aromatase is responsible for the synthesis of E2. Remodelled pulmonary arteries, lesions and human pulmonary artery smooth muscle cells (hPASMCs) from PAH patients have high levels of aromatase. CYP1B1 can convert E2 to mitogenic 16-hydroxy-estrogens (16OHEs) and this enzyme is over-expressed in diseased pulmonary arteries from PAH patients. Existing assays have not been sensitive or specific enough to detect levels of many E2 metabolites in PAH patient blood. Using a newly developed liquid chromatography tandem mass spectrometry (LC-MS/MS) assay, here we investigate the profile of several E2 metabolites in iPAH patients.

Original language	English
Number of pages	5
Journal	Pulmonary Circulation
Volume	10
Issue number	1
Early online date	13 Feb 2020
DOIs	https://doi.org/10.1177/2045894020908783
Publication status	E-pub ahead of print - 13 Feb 2020

Keywords

idiopathic pulmonary arterial hypertension (iPAH)
plasma estradiol (E2)
postmenopausal women
estrogen

Access to Document

10.1177/2045894020908783Licence: CC BY 4.0

Denver-etal-PC-2020-Estrogen-metabolites-in-patients-with-idiopathic-pulmonary-arterial-hypertensionFinal published version, 197 KBLicence: CC BY 4.0

1 Active

RG/16/2/32153: Sex and the development of pulmonary arterial hypertension. BHF Programme transfer.
MacLean, M.
British Heart Foundation BHF
25/02/19 → 31/01/22
Project: Research

Cite this

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abstract = "Increased risk and severity of idiopathic pulmonary arterial hypertension (iPAH) is associated with elevated plasma estradiol (E2) in both men and postmenopausal women, suggesting that E2 is not ovarian-derived. Aromatase is responsible for the synthesis of E2. Remodelled pulmonary arteries, lesions and human pulmonary artery smooth muscle cells (hPASMCs) from PAH patients have high levels of aromatase. CYP1B1 can convert E2 to mitogenic 16-hydroxy-estrogens (16OHEs) and this enzyme is over-expressed in diseased pulmonary arteries from PAH patients. Existing assays have not been sensitive or specific enough to detect levels of many E2 metabolites in PAH patient blood. Using a newly developed liquid chromatography tandem mass spectrometry (LC-MS/MS) assay, here we investigate the profile of several E2 metabolites in iPAH patients.",

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AU - Denver, Nina

AU - Homer, Natalie Z.M.

AU - Andrew, Ruth

AU - Harvey, Katie Y.

AU - Morrell, Nicholas

AU - Austin, Eric D.

AU - MacLean, Margaret R.

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AB - Increased risk and severity of idiopathic pulmonary arterial hypertension (iPAH) is associated with elevated plasma estradiol (E2) in both men and postmenopausal women, suggesting that E2 is not ovarian-derived. Aromatase is responsible for the synthesis of E2. Remodelled pulmonary arteries, lesions and human pulmonary artery smooth muscle cells (hPASMCs) from PAH patients have high levels of aromatase. CYP1B1 can convert E2 to mitogenic 16-hydroxy-estrogens (16OHEs) and this enzyme is over-expressed in diseased pulmonary arteries from PAH patients. Existing assays have not been sensitive or specific enough to detect levels of many E2 metabolites in PAH patient blood. Using a newly developed liquid chromatography tandem mass spectrometry (LC-MS/MS) assay, here we investigate the profile of several E2 metabolites in iPAH patients.

KW - idiopathic pulmonary arterial hypertension (iPAH)

KW - plasma estradiol (E2)

KW - postmenopausal women

KW - estrogen

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Estrogen metabolites in a small cohort of patients with idiopathic pulmonary arterial hypertension

Abstract

Keywords

Access to Document

RG/16/2/32153: Sex and the development of pulmonary arterial hypertension. BHF Programme transfer.

Cite this