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; Merz, Tobias and Pichler Hefti, Jacqueline Renée

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:

12 Feb 2018 16:34

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

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