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

Denver, Nina and Homer, Natalie Z.M. and Andrew, Ruth and Harvey, Katie Y. and Morrell, Nicholas and Austin, Eric D. and MacLean, Margaret R. (2020) Estrogen metabolites in a small cohort of patients with idiopathic pulmonary arterial hypertension. Pulmonary Circulation, 10 (1). ISSN 2045-8940

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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.