S38 Hepcidin treatment of human pulmonary artery smooth muscle cells and mitochondrial dysfunction. (December 2018)

• Record Type: Journal Article
• Authors: Issitt, T; Toe, Q; Quinlan, G; Wort, SJ
• Is Part Of: Thorax. Volume 73(2018)Supplement 4
• Page Start: A23
• Page End: A24
• Publication Date: 2018-12
• Subjects: Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thorax-2018-212555.44
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : Introduction: Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular remodelling, increased vascular resistance and right ventricular failure. Dysregulation of iron homeostasis and increased proliferation in PAH have been linked to the iron-regulatory hormone hepcidin. Research from our lab has recently shown that hepcidin treatment in human pulmonary arterial smooth muscle cells (hPASMC) leads to an increased proliferative response possibly mediated by the haemoglobin (Hb) scavenger CD163. Objectives: This study aims to characterise mitochondrial dysregulation in hPASMCs in relation to changes in iron homeostasis following treatment with hepcidin or haemoglobin. Methods: hPASMCs were treated with hepcidin (1 µg/ml), IL-6 (10 ng/ml) and haemoglobin (3 µM) for 24 hours. Immunofluorescence of mitochondrial markers were analysed to assess changes to volume and intensity. Results: Our findings indicate significant morphological changes with a 2 fold decrease in average mitochondrial volume following 24 hours of treatment with hepcidin or IL-6. In addition, haemoglobin treatment produced significant phenotypic changes with no significant change in volume or amount of mitochondria. Conclusion: The findings presented here indicate that alterations in iron homeostasis influence global metabolism through mitochondrial dysfunction. This work presents novel insight into mitochondrial dynamics in relation to hepcidin driven proliferation in PAH.