Screening for potential targets to reduce stenosis in bioprosthetic heart valves

Abstract Progressive stenosis is one of the main factors that limit the lifetime of bioprosthetic valved conduits. To improve long-term performance we aimed to identify targets that inhibit pannus formation on conduit walls. From 11 explanted, obstructed, RNAlater presevered pulmonary valved conduit...

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Autores principales:	Rudi Foth, Orr Shomroni, Matthias Sigler, Jürgen Hörer, Julie Cleuziou, Thomas Paul, Katja Eildermann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1f33da6d90bd4a3a833e48c421713655
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spelling	oai:doaj.org-article:1f33da6d90bd4a3a833e48c4217136552021-12-02T13:57:26ZScreening for potential targets to reduce stenosis in bioprosthetic heart valves10.1038/s41598-021-81340-22045-2322https://doaj.org/article/1f33da6d90bd4a3a833e48c4217136552021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81340-2https://doaj.org/toc/2045-2322Abstract Progressive stenosis is one of the main factors that limit the lifetime of bioprosthetic valved conduits. To improve long-term performance we aimed to identify targets that inhibit pannus formation on conduit walls. From 11 explanted, obstructed, RNAlater presevered pulmonary valved conduits, we dissected the thickened conduit wall and the thin leaflet to determine gene expression-profiles using ultra deep sequencing. Differential gene expression between pannus and leaflet provided the dataset that was screened for potential targets. Promising target candidates were immunohistologically stained to see protein abundance and the expressing cell type(s). While immunostainings for DDR2 and FGFR2 remained inconclusive, EGFR, ErbB4 and FLT4 were specifically expressed in a subset of tissue macrophages, a cell type known to regulate the initiation, maintenance, and resolution of tissue repair. Taken toghether, our data suggest EGFR, ErbB4 and FLT4 as potential target candidates to limit pannus formation in bioprosthestic replacement valves.Rudi FothOrr ShomroniMatthias SiglerJürgen HörerJulie CleuziouThomas PaulKatja EildermannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rudi Foth Orr Shomroni Matthias Sigler Jürgen Hörer Julie Cleuziou Thomas Paul Katja Eildermann Screening for potential targets to reduce stenosis in bioprosthetic heart valves
description	Abstract Progressive stenosis is one of the main factors that limit the lifetime of bioprosthetic valved conduits. To improve long-term performance we aimed to identify targets that inhibit pannus formation on conduit walls. From 11 explanted, obstructed, RNAlater presevered pulmonary valved conduits, we dissected the thickened conduit wall and the thin leaflet to determine gene expression-profiles using ultra deep sequencing. Differential gene expression between pannus and leaflet provided the dataset that was screened for potential targets. Promising target candidates were immunohistologically stained to see protein abundance and the expressing cell type(s). While immunostainings for DDR2 and FGFR2 remained inconclusive, EGFR, ErbB4 and FLT4 were specifically expressed in a subset of tissue macrophages, a cell type known to regulate the initiation, maintenance, and resolution of tissue repair. Taken toghether, our data suggest EGFR, ErbB4 and FLT4 as potential target candidates to limit pannus formation in bioprosthestic replacement valves.
format	article
author	Rudi Foth Orr Shomroni Matthias Sigler Jürgen Hörer Julie Cleuziou Thomas Paul Katja Eildermann
author_facet	Rudi Foth Orr Shomroni Matthias Sigler Jürgen Hörer Julie Cleuziou Thomas Paul Katja Eildermann
author_sort	Rudi Foth
title	Screening for potential targets to reduce stenosis in bioprosthetic heart valves
title_short	Screening for potential targets to reduce stenosis in bioprosthetic heart valves
title_full	Screening for potential targets to reduce stenosis in bioprosthetic heart valves
title_fullStr	Screening for potential targets to reduce stenosis in bioprosthetic heart valves
title_full_unstemmed	Screening for potential targets to reduce stenosis in bioprosthetic heart valves
title_sort	screening for potential targets to reduce stenosis in bioprosthetic heart valves
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1f33da6d90bd4a3a833e48c421713655
work_keys_str_mv	AT rudifoth screeningforpotentialtargetstoreducestenosisinbioprostheticheartvalves AT orrshomroni screeningforpotentialtargetstoreducestenosisinbioprostheticheartvalves AT matthiassigler screeningforpotentialtargetstoreducestenosisinbioprostheticheartvalves AT jurgenhorer screeningforpotentialtargetstoreducestenosisinbioprostheticheartvalves AT juliecleuziou screeningforpotentialtargetstoreducestenosisinbioprostheticheartvalves AT thomaspaul screeningforpotentialtargetstoreducestenosisinbioprostheticheartvalves AT katjaeildermann screeningforpotentialtargetstoreducestenosisinbioprostheticheartvalves
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Screening for potential targets to reduce stenosis in bioprosthetic heart valves

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