Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue

Abstract Afterload enhancement (AE) of rat engineered heart tissue (EHT) in vitro leads to a multitude of changes that in vivo are referred to as pathological cardiac hypertrophy: e.g., cardiomyocyte hypertrophy, contractile dysfunction, reactivation of fetal genes and fibrotic changes. Moreover AE...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tessa R. Werner, Ann-Cathrin Kunze, Justus Stenzig, Thomas Eschenhagen, Marc N. Hirt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0fa1711dc2dc4da28a62e632b28a965e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0fa1711dc2dc4da28a62e632b28a965e
record_format	dspace
spelling	oai:doaj.org-article:0fa1711dc2dc4da28a62e632b28a965e2021-12-02T15:08:10ZBlockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue10.1038/s41598-019-46818-02045-2322https://doaj.org/article/0fa1711dc2dc4da28a62e632b28a965e2019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46818-0https://doaj.org/toc/2045-2322Abstract Afterload enhancement (AE) of rat engineered heart tissue (EHT) in vitro leads to a multitude of changes that in vivo are referred to as pathological cardiac hypertrophy: e.g., cardiomyocyte hypertrophy, contractile dysfunction, reactivation of fetal genes and fibrotic changes. Moreover AE induced the upregulation of 22 abundantly expressed microRNAs. Here, we aimed at evaluating the functional effect of inhibiting 7 promising microRNAs (miR-21-5p, miR-146b-5p, miR-31a-5p, miR-322-5p, miR-450a-5p, miR-140-3p and miR-132-3p) in a small-range screen. Singular transfection of locked nucleic acid (LNA)-based anti-miRs at 100 nM (before the one week AE-procedure) led to a powerful reduction of the targeted microRNAs. Pretreatment with anti-miR-146b-5p, anti-miR-322-5p or anti-miR-450a-5p did not alter the AE-induced contractile decline, while anti-miR-31a-5p-pretreatment even worsened it. Anti-miR-21-5p and anti-miR-132-3p partially attenuated the AE-effect, confirming previous reports. LNA-anti-miR against miR-140-3p, a microRNA recently identified as a prognostic biomarker of cardiovascular disease, also attenuated the AE-effect. To simplify future in vitro experiments and to create an inhibitor for in vivo applications, we designed shorter miR-140-3p-inhibitors and encountered variable efficiency. Only the inhibitor that effectively repressed miR-140-3p was also protective against the AE-induced contractile decline. In summary, in a small-range functional screen, miR-140-3p evolved as a possible new target for the attenuation of afterload-induced pathological cardiac hypertrophy.Tessa R. WernerAnn-Cathrin KunzeJustus StenzigThomas EschenhagenMarc N. HirtNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tessa R. Werner Ann-Cathrin Kunze Justus Stenzig Thomas Eschenhagen Marc N. Hirt Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue
description	Abstract Afterload enhancement (AE) of rat engineered heart tissue (EHT) in vitro leads to a multitude of changes that in vivo are referred to as pathological cardiac hypertrophy: e.g., cardiomyocyte hypertrophy, contractile dysfunction, reactivation of fetal genes and fibrotic changes. Moreover AE induced the upregulation of 22 abundantly expressed microRNAs. Here, we aimed at evaluating the functional effect of inhibiting 7 promising microRNAs (miR-21-5p, miR-146b-5p, miR-31a-5p, miR-322-5p, miR-450a-5p, miR-140-3p and miR-132-3p) in a small-range screen. Singular transfection of locked nucleic acid (LNA)-based anti-miRs at 100 nM (before the one week AE-procedure) led to a powerful reduction of the targeted microRNAs. Pretreatment with anti-miR-146b-5p, anti-miR-322-5p or anti-miR-450a-5p did not alter the AE-induced contractile decline, while anti-miR-31a-5p-pretreatment even worsened it. Anti-miR-21-5p and anti-miR-132-3p partially attenuated the AE-effect, confirming previous reports. LNA-anti-miR against miR-140-3p, a microRNA recently identified as a prognostic biomarker of cardiovascular disease, also attenuated the AE-effect. To simplify future in vitro experiments and to create an inhibitor for in vivo applications, we designed shorter miR-140-3p-inhibitors and encountered variable efficiency. Only the inhibitor that effectively repressed miR-140-3p was also protective against the AE-induced contractile decline. In summary, in a small-range functional screen, miR-140-3p evolved as a possible new target for the attenuation of afterload-induced pathological cardiac hypertrophy.
format	article
author	Tessa R. Werner Ann-Cathrin Kunze Justus Stenzig Thomas Eschenhagen Marc N. Hirt
author_facet	Tessa R. Werner Ann-Cathrin Kunze Justus Stenzig Thomas Eschenhagen Marc N. Hirt
author_sort	Tessa R. Werner
title	Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue
title_short	Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue
title_full	Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue
title_fullStr	Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue
title_full_unstemmed	Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue
title_sort	blockade of mir-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/0fa1711dc2dc4da28a62e632b28a965e
work_keys_str_mv	AT tessarwerner blockadeofmir1403ppreventsfunctionaldeteriorationinafterloadenhancedengineeredhearttissue AT anncathrinkunze blockadeofmir1403ppreventsfunctionaldeteriorationinafterloadenhancedengineeredhearttissue AT justusstenzig blockadeofmir1403ppreventsfunctionaldeteriorationinafterloadenhancedengineeredhearttissue AT thomaseschenhagen blockadeofmir1403ppreventsfunctionaldeteriorationinafterloadenhancedengineeredhearttissue AT marcnhirt blockadeofmir1403ppreventsfunctionaldeteriorationinafterloadenhancedengineeredhearttissue
_version_	1718388234273161216

Blockade of miR-140-3p prevents functional deterioration in afterload-enhanced engineered heart tissue

Ejemplares similares