Urine peptidome analysis in cardiorenal syndrome reflects molecular processes

Abstract The cardiorenal syndrome (CRS) is defined as the confluence of heart-kidney dysfunction. This study investigates the molecular differences at the level of the urinary peptidome between CRS patients and controls and their association to disease pathophysiology. The urinary peptidome of CRS p...

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Autores principales:	Eleni Petra, Tianlin He, Vasiliki Lygirou, Agnieszka Latosinska, Harald Mischak, Antonia Vlahou, Joachim Jankowski
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bd1fd87424a543878fa977fe627fdbdc
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spelling	oai:doaj.org-article:bd1fd87424a543878fa977fe627fdbdc2021-12-02T15:08:11ZUrine peptidome analysis in cardiorenal syndrome reflects molecular processes10.1038/s41598-021-95695-z2045-2322https://doaj.org/article/bd1fd87424a543878fa977fe627fdbdc2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95695-zhttps://doaj.org/toc/2045-2322Abstract The cardiorenal syndrome (CRS) is defined as the confluence of heart-kidney dysfunction. This study investigates the molecular differences at the level of the urinary peptidome between CRS patients and controls and their association to disease pathophysiology. The urinary peptidome of CRS patients (n = 353) was matched for age and sex with controls (n = 356) at a 1:1 ratio. Changes in the CRS peptidome versus controls were identified after applying the Mann–Whitney test, followed by correction for multiple testing. Proteasix tool was applied to investigate predicted proteases involved in CRS-associated peptide generation. Overall, 559 differentially excreted urinary peptides were associated with CRS patients. Of these, 193 peptides were specifically found in CRS when comparing with heart failure and chronic kidney disease urinary peptide profiles. Proteasix predicted 18 proteases involved in > 1% of proteolytic cleavage events including multiple forms of MMPs, proprotein convertases, cathepsins and kallikrein 4. Forty-four percent of the cleavage events were produced by 3 proteases including MMP13, MMP9 and MMP2. Pathway enrichment analysis supported that ECM-related pathways, fibrosis and inflammation were represented. Collectively, our study describes the changes in urinary peptides of CRS patients and potential proteases involved in their generation, laying the basis for further validation.Eleni PetraTianlin HeVasiliki LygirouAgnieszka LatosinskaHarald MischakAntonia VlahouJoachim JankowskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eleni Petra Tianlin He Vasiliki Lygirou Agnieszka Latosinska Harald Mischak Antonia Vlahou Joachim Jankowski Urine peptidome analysis in cardiorenal syndrome reflects molecular processes
description	Abstract The cardiorenal syndrome (CRS) is defined as the confluence of heart-kidney dysfunction. This study investigates the molecular differences at the level of the urinary peptidome between CRS patients and controls and their association to disease pathophysiology. The urinary peptidome of CRS patients (n = 353) was matched for age and sex with controls (n = 356) at a 1:1 ratio. Changes in the CRS peptidome versus controls were identified after applying the Mann–Whitney test, followed by correction for multiple testing. Proteasix tool was applied to investigate predicted proteases involved in CRS-associated peptide generation. Overall, 559 differentially excreted urinary peptides were associated with CRS patients. Of these, 193 peptides were specifically found in CRS when comparing with heart failure and chronic kidney disease urinary peptide profiles. Proteasix predicted 18 proteases involved in > 1% of proteolytic cleavage events including multiple forms of MMPs, proprotein convertases, cathepsins and kallikrein 4. Forty-four percent of the cleavage events were produced by 3 proteases including MMP13, MMP9 and MMP2. Pathway enrichment analysis supported that ECM-related pathways, fibrosis and inflammation were represented. Collectively, our study describes the changes in urinary peptides of CRS patients and potential proteases involved in their generation, laying the basis for further validation.
format	article
author	Eleni Petra Tianlin He Vasiliki Lygirou Agnieszka Latosinska Harald Mischak Antonia Vlahou Joachim Jankowski
author_facet	Eleni Petra Tianlin He Vasiliki Lygirou Agnieszka Latosinska Harald Mischak Antonia Vlahou Joachim Jankowski
author_sort	Eleni Petra
title	Urine peptidome analysis in cardiorenal syndrome reflects molecular processes
title_short	Urine peptidome analysis in cardiorenal syndrome reflects molecular processes
title_full	Urine peptidome analysis in cardiorenal syndrome reflects molecular processes
title_fullStr	Urine peptidome analysis in cardiorenal syndrome reflects molecular processes
title_full_unstemmed	Urine peptidome analysis in cardiorenal syndrome reflects molecular processes
title_sort	urine peptidome analysis in cardiorenal syndrome reflects molecular processes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bd1fd87424a543878fa977fe627fdbdc
work_keys_str_mv	AT elenipetra urinepeptidomeanalysisincardiorenalsyndromereflectsmolecularprocesses AT tianlinhe urinepeptidomeanalysisincardiorenalsyndromereflectsmolecularprocesses AT vasilikilygirou urinepeptidomeanalysisincardiorenalsyndromereflectsmolecularprocesses AT agnieszkalatosinska urinepeptidomeanalysisincardiorenalsyndromereflectsmolecularprocesses AT haraldmischak urinepeptidomeanalysisincardiorenalsyndromereflectsmolecularprocesses AT antoniavlahou urinepeptidomeanalysisincardiorenalsyndromereflectsmolecularprocesses AT joachimjankowski urinepeptidomeanalysisincardiorenalsyndromereflectsmolecularprocesses
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Urine peptidome analysis in cardiorenal syndrome reflects molecular processes

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