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

Abstract

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.

Autoren

Lipps
Northe
Figueiredo
Rohde
Brahmer
Krämer-Albers
Liebetrau
Wiedenroth
Mayer
Kriechbaum
Dörr
Nef
Hamm
Keller
Troidl

DOI

10.3390/biom9110666

eISSN

2218-273X

Ausgabe der Veröffentlichung

11

Zeitschrift

Biomolecules

Sprache

en

Online publication date

2019

Paginierung

666 - 666

Status

Published online

Herausgeber

MDPI AG

Herausgeber URL

http://dx.doi.org/10.3390/biom9110666

Datum der Datenerfassung

2020

Titel

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

Ausgabe der Zeitschrift

9

Datenquelle: Crossref

Abstract

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.

Addresses

Medical Clinics I-Cardiology and Angiology, Justus-Liebig-University Giessen, 35392 Giessen, Germany. christoph.lipps@innere.med.uni-giessen.de.

Autoren

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

DOI

10.3390/biom9110666

eISSN

2218-273X

Externe Identifier

PubMed Identifier: 31671920
PubMed Central ID: PMC6920761

Funding acknowledgements

Deutsche Forschungsgemeinschaft: SFB 1213 –“Pulmonale Hypertonie und Cor pulmonale”

Open access

true

ISSN

2218-273X

Ausgabe der Veröffentlichung

11

Zeitschrift

Biomolecules

Schlüsselwörter

Humans
Hypertension, Pulmonary
Case-Control Studies
Aged
Middle Aged
Female
Male
RNA, Small Untranslated
Extracellular Vesicles

Sprache

eng

Medium

Electronic

Online publication date

2019

Open access status

Open Access

Paginierung

E666

Datum der Veröffentlichung

2019

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2019

Titel

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

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

9

Files

https://www.mdpi.com/2218-273X/9/11/666/pdf?version=1573265314 https://europepmc.org/articles/PMC6920761?pdf=render

Datenquelle: Europe PubMed Central

Abstract

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.

Date of acceptance

2019

Autoren

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

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/31671920

DOI

10.3390/biom9110666

eISSN

2218-273X

Externe Identifier

PubMed Central ID: PMC6920761

Ausgabe der Veröffentlichung

11

Zeitschrift

Biomolecules

Schlüsselwörter

biomarker
chronic thromboembolic pulmonary hypertension
extracellular vesicles
pulmonary disease
right heart dysfunction
small non-coding RNA
Aged
Case-Control Studies
Extracellular Vesicles
Female
Humans
Hypertension, Pulmonary
Male
Middle Aged
RNA, Small Untranslated

Sprache

eng

Country

Switzerland

PII

biom9110666

Datum der Veröffentlichung

2019

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2020

Titel

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

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

9

Datenquelle: PubMed

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

Files

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