Blissenbach, Birgit, Nakas, Christos T., Kroenke, Martin, Geiser, Thomas, Merz, Tobias M. and Hefti, Jacqueline Pichler (2018). Hypoxia-induced changes in plasma micro-RNAs correlate with pulmonary artery pressure at high altitude. Am. J. Physiol.-Lung Cell. Mol. Physiol., 314 (1). S. L157 - 8. BETHESDA: AMER PHYSIOLOGICAL SOC. ISSN 1522-1504

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Abstract

In vitro and animal studies revealed micro-RNAs (miRs) to be involved in modulation of hypoxia-induced pulmonary hypertension (HPH). However, knowledge of circulating miRs in humans in the context of HPH is very limited. Since symptoms of HPH are nonspecific and noninvasive 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. Forty healthy volunteers were repetitively examined during a high-altitude expedition up to an altitude of 7,050 m. Plasma levels of miR-17, -21, and -190 were measured by real-time quantitative 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 with baseline at 500 m, miR-17 changed by 4.72 +/- 0.57-fold, miR-21 changed by 1.91 +/- 0.33-fold, and miR-190 changed by 3.61 +/- 0.54-fold at 7,050 m (means +/- SD). Even after adjusting for hypoxemia, miR-17 and miR-190 were found to be independently correlated with increased SPAP. Progressive hypobaric hypoxia significantly affects levels of circulating miR-17, -21, and -190. Independently from the extent of hypoxemia, miR-17 and -190 significantly correlate with increased SPAP. These novel findings provide evidence for an epigenetic modulation of hypoxia-induced increase in pulmonary artery pressures by miR-17 and -190 and suggest the potential value of these miRs as biomarkers for HPH.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Blissenbach, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nakas, Christos T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroenke, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geiser, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merz, Tobias M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hefti, Jacqueline PichlerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-203446
DOI: 10.1152/ajplung.00146.2017
Journal or Publication Title: Am. J. Physiol.-Lung Cell. Mol. Physiol.
Volume: 314
Number: 1
Page Range: S. L157 - 8
Date: 2018
Publisher: AMER PHYSIOLOGICAL SOC
Place of Publication: BETHESDA
ISSN: 1522-1504
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SMOOTH-MUSCLE-CELLS; HYPERTENSION; CLUSTER; PROTEIN; VASOCONSTRICTION; MECHANISMS; CROSSTALK; PATHWAYS; FIBROSIS; DISEASEMultiple languages
Physiology; Respiratory SystemMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/20344

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