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

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 ext...

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Príomhchruthaitheoirí: Christoph Lipps, Philipp Northe, Ricardo Figueiredo, Manfred Rohde, Alexandra Brahmer, Eva-Maria Krämer-Albers, Christoph Liebetrau, Christoph B. Wiedenroth, Eckhard Mayer, Steffen D. Kriechbaum, Oliver Dörr, Holger Nef, Christian W. Hamm, Till Keller, Christian Troidl
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Teanga:English
Foilsithe / Cruthaithe: MDPI AG 2019-10-01
Sraith:Biomolecules
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Rochtain ar líne:https://www.mdpi.com/2218-273X/9/11/666
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author Christoph Lipps
Philipp Northe
Ricardo Figueiredo
Manfred Rohde
Alexandra Brahmer
Eva-Maria Krämer-Albers
Christoph Liebetrau
Christoph B. Wiedenroth
Eckhard Mayer
Steffen D. Kriechbaum
Oliver Dörr
Holger Nef
Christian W. Hamm
Till Keller
Christian Troidl
author_facet Christoph Lipps
Philipp Northe
Ricardo Figueiredo
Manfred Rohde
Alexandra Brahmer
Eva-Maria Krämer-Albers
Christoph Liebetrau
Christoph B. Wiedenroth
Eckhard Mayer
Steffen D. Kriechbaum
Oliver Dörr
Holger Nef
Christian W. Hamm
Till Keller
Christian Troidl
author_sort Christoph Lipps
collection DOAJ
description 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.
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spelling doaj.art-4c0f9376ee5d45c99a7ab4994ffb51192022-12-21T19:40:53ZengMDPI AGBiomolecules2218-273X2019-10-0191166610.3390/biom9110666biom9110666Non-Invasive Approach for Evaluation of Pulmonary Hypertension Using Extracellular Vesicle-Associated Small Non-Coding RNAChristoph Lipps0Philipp Northe1Ricardo Figueiredo2Manfred Rohde3Alexandra Brahmer4Eva-Maria Krämer-Albers5Christoph Liebetrau6Christoph B. Wiedenroth7Eckhard Mayer8Steffen D. Kriechbaum9Oliver Dörr10Holger Nef11Christian W. Hamm12Till Keller13Christian Troidl14Medical Clinics I-Cardiology and Angiology, Justus-Liebig-University Giessen, 35392 Giessen, GermanyMedical Clinics I-Cardiology and Angiology, Justus-Liebig-University Giessen, 35392 Giessen, GermanyGenXPro GmbH, 60438 Frankfurt am Main, GermanyCentral Facility for Microscopy, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyInstitute of Developmental Biology and Neurobiology, Biology of Extracellular Vesicles, Johannes Gutenberg-University, 55122 Mainz, GermanyInstitute of Developmental Biology and Neurobiology, Biology of Extracellular Vesicles, Johannes Gutenberg-University, 55122 Mainz, GermanyDepartment of Cardiology, Kerckhoff Clinic GmbH, 61231 Bad Nauheim, GermanyDepartment of Thoracic Surgery, Kerckhoff Clinic GmbH, 61231 Bad Nauheim, GermanyDepartment of Thoracic Surgery, Kerckhoff Clinic GmbH, 61231 Bad Nauheim, GermanyDepartment of Cardiology, Kerckhoff Clinic GmbH, 61231 Bad Nauheim, GermanyMedical Clinics I-Cardiology and Angiology, Justus-Liebig-University Giessen, 35392 Giessen, GermanyMedical Clinics I-Cardiology and Angiology, Justus-Liebig-University Giessen, 35392 Giessen, GermanyMedical Clinics I-Cardiology and Angiology, Justus-Liebig-University Giessen, 35392 Giessen, GermanyMedical Clinics I-Cardiology and Angiology, Justus-Liebig-University Giessen, 35392 Giessen, GermanyMedical Clinics I-Cardiology and Angiology, Justus-Liebig-University Giessen, 35392 Giessen, GermanyExtracellular 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.https://www.mdpi.com/2218-273X/9/11/666biomarkerextracellular vesiclessmall non-coding rnapulmonary diseaseright heart dysfunctionchronic thromboembolic pulmonary hypertension
spellingShingle Christoph Lipps
Philipp Northe
Ricardo Figueiredo
Manfred Rohde
Alexandra Brahmer
Eva-Maria Krämer-Albers
Christoph Liebetrau
Christoph B. Wiedenroth
Eckhard Mayer
Steffen D. Kriechbaum
Oliver Dörr
Holger Nef
Christian W. Hamm
Till Keller
Christian Troidl
Non-Invasive Approach for Evaluation of Pulmonary Hypertension Using Extracellular Vesicle-Associated Small Non-Coding RNA
Biomolecules
biomarker
extracellular vesicles
small non-coding rna
pulmonary disease
right heart dysfunction
chronic thromboembolic pulmonary hypertension
title Non-Invasive Approach for Evaluation of Pulmonary Hypertension Using Extracellular Vesicle-Associated Small Non-Coding RNA
title_full Non-Invasive Approach for Evaluation of Pulmonary Hypertension Using Extracellular Vesicle-Associated Small Non-Coding RNA
title_fullStr Non-Invasive Approach for Evaluation of Pulmonary Hypertension Using Extracellular Vesicle-Associated Small Non-Coding RNA
title_full_unstemmed Non-Invasive Approach for Evaluation of Pulmonary Hypertension Using Extracellular Vesicle-Associated Small Non-Coding RNA
title_short Non-Invasive Approach for Evaluation of Pulmonary Hypertension Using Extracellular Vesicle-Associated Small Non-Coding RNA
title_sort non invasive approach for evaluation of pulmonary hypertension using extracellular vesicle associated small non coding rna
topic biomarker
extracellular vesicles
small non-coding rna
pulmonary disease
right heart dysfunction
chronic thromboembolic pulmonary hypertension
url https://www.mdpi.com/2218-273X/9/11/666
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