Hypoxia-induced changes in plasma microRNAs correlate with pulmonary artery pressure at high altitude.

Blissenbach, Birgit; Nakas, Christos T.; Krönke, Martin; Geiser, Thomas; Merz, Tobias; Pichler Hefti, Jacqueline Renée (2018). Hypoxia-induced changes in plasma microRNAs correlate with pulmonary artery pressure at high altitude. American journal of physiology - lung cellular and molecular physiology, 314(1), L157-L164. American Physiological Society 10.1152/ajplung.00146.2017

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In vitro and animal studies revealed miRs to be involved in modulation of hypoxia-induced pulmonary hypertension (HPH). However, knowledge on circulating miRs in humans in the context of HPH is very limited. Since symptoms of HPH are non-specific and non-invasive diagnostic parameters do not exist, a disease-specific and hypoxemia-independent biomarker indicating HPH would be of clinical value. To examine whether plasma miR levels correlate with hypoxia-induced increase in pulmonary artery pressures, plasma miRs were assessed in a model of hypoxia-related pulmonary hypertension in humans exposed to extreme altitude. 40 healthy volunteers were repetitively examined during a high altitude expedition up to an altitude of 7050m. Plasma levels of miR-17, -21 and -190 were measured by quantitative Real-time (qRT)-PCR and correlated with systolic pulmonary artery pressure (SPAP), which was assessed by echocardiography. A significant altitude-dependent increase in circulating miR expression was found (all p-values <0.0001). Compared to baseline at 500m, miR-17 changed by 4.72 ± 0.57 fold, miR-21 by 1.91 ± 0.33, and miR-190 by 3.61 ± 0.54 fold at 7050m. MiR-17 and miR-190 were found to be independently correlated with increased SPAP, even after adjusting for hypoxemia. Progressive hypobaric hypoxia significantly affects levels of circulating miR-17, -21, and -190. MiR-17 and -190 significantly correlate with increased SPAP, independently from the extent of hypoxemia. These novel findings provide evidence for an epigenetic modulation of hypoxia-induced increase in pulmonary artery pressures by miR-17 and -190 and suggest a potential value of these miRs as biomarkers for HPH.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology 04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry 04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
UniBE Contributor:	Nakas, Christos T., Geiser, Thomas (A), Merz, Tobias, Pichler, Jacqueline
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1040-0605
Publisher:	American Physiological Society
Language:	English
Submitter:	Rahel Holderegger
Date Deposited:	27 Nov 2017 11:14
Last Modified:	29 Mar 2023 23:35
Publisher DOI:	10.1152/ajplung.00146.2017
PubMed ID:	28971974
Uncontrolled Keywords:	high altitude hypoxia plasma microRNA pulmonary artery pressure
URI:	https://boris.unibe.ch/id/eprint/106588