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Open AccessArticle

Non-Invasive Approach for Evaluation of Pulmonary Hypertension Using Extracellular Vesicle-Associated Small Non-Coding RNA

1
Medical Clinics I-Cardiology and Angiology, Justus-Liebig-University Giessen, 35392 Giessen, Germany
2
Department of Cardiology, Kerckhoff Clinic GmbH, 61231 Bad Nauheim, Germany
3
German Centre for Cardiovascular Research, Partner Site Rhine-Main, 61231 Bad Nauheim, Germany
4
GenXPro GmbH, 60438 Frankfurt am Main, Germany
5
Central Facility for Microscopy, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
6
Institute of Developmental Biology and Neurobiology, Biology of Extracellular Vesicles, Johannes Gutenberg-University, 55122 Mainz, Germany
7
Department of Thoracic Surgery, Kerckhoff Clinic GmbH, 61231 Bad Nauheim, Germany
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 666; https://doi.org/10.3390/biom9110666
Received: 4 October 2019 / Revised: 27 October 2019 / Accepted: 28 October 2019 / Published: 29 October 2019
(This article belongs to the Special Issue Molecular Mechanisms of Lung Diseases)
Extracellular vesicles are released by numerous cell types of the human body under physiological but also under pathophysiological conditions. They are important for cell–cell communication and carry specific signatures of peptides and RNAs. In this study, we aimed to determine whether extracellular vesicles isolated from patients with pulmonary hypertension show a disease specific signature of small non-coding RNAs and thus have the potential to serve as diagnostic and prognostic biomarkers. Extracellular vesicles were isolated from the serum of 23 patients with chronic thromboembolic pulmonary hypertension (CTEPH) and 23 controls using two individual methods: a column-based method or by precipitation. Extracellular vesicle- associated RNAs were analyzed by next-generation sequencing applying molecular barcoding, and differentially expressed small non-coding RNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). We identified 18 microRNAs and 21 P-element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) or piRNA clusters that were differentially expressed in CTEPH patients compared with controls. Bioinformatic analysis predicted a contribution of these piRNAs to the progression of cardiac and vascular remodeling. Expression levels of DQ593039 correlated with clinically meaningful parameters such as mean pulmonary arterial pressure, pulmonary vascular resistance, right ventricular systolic pressure, and levels of N-terminal pro-brain natriuretic peptide. Thus, we identified the extracellular vesicle- derived piRNA, DQ593039, as a potential biomarker for pulmonary hypertension and right heart disease. View Full-Text
Keywords: biomarker; extracellular vesicles; small non-coding RNA; pulmonary disease; right heart dysfunction; chronic thromboembolic pulmonary hypertension biomarker; extracellular vesicles; small non-coding RNA; pulmonary disease; right heart dysfunction; chronic thromboembolic pulmonary hypertension
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Lipps, C.; Northe, P.; Figueiredo, R.; Rohde, M.; Brahmer, A.; Krämer-Albers, E.-M.; Liebetrau, C.; Wiedenroth, C.B.; Mayer, E.; Kriechbaum, S.D.; Dörr, O.; Nef, H.; Hamm, C.W.; Keller, T.; Troidl, C. Non-Invasive Approach for Evaluation of Pulmonary Hypertension Using Extracellular Vesicle-Associated Small Non-Coding RNA. Biomolecules 2019, 9, 666.

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