Altered microRNA and mRNA profiles during heart failure in the human sinoatrial node

Abstract Heart failure (HF) is frequently accompanied with the sinoatrial node (SAN) dysfunction, which causes tachy-brady arrhythmias and increased mortality. MicroRNA (miR) alterations are associated with HF progression. However, the transcriptome of HF human SAN, and its role in HF-associated rem...

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Autores principales:	Ning Li, Esthela Artiga, Anuradha Kalyanasundaram, Brian J. Hansen, Amy Webb, Maciej Pietrzak, Brandon Biesiadecki, Bryan Whitson, Nahush A. Mokadam, Paul M. L. Janssen, John D. Hummel, Peter J. Mohler, Halina Dobrzynski, Vadim V. Fedorov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d1f3400a06c3430697951538c406b0ec
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spelling	oai:doaj.org-article:d1f3400a06c3430697951538c406b0ec2021-12-02T17:37:40ZAltered microRNA and mRNA profiles during heart failure in the human sinoatrial node10.1038/s41598-021-98580-x2045-2322https://doaj.org/article/d1f3400a06c3430697951538c406b0ec2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98580-xhttps://doaj.org/toc/2045-2322Abstract Heart failure (HF) is frequently accompanied with the sinoatrial node (SAN) dysfunction, which causes tachy-brady arrhythmias and increased mortality. MicroRNA (miR) alterations are associated with HF progression. However, the transcriptome of HF human SAN, and its role in HF-associated remodeling of ion channels, transporters, and receptors responsible for SAN automaticity and conduction impairments is unknown. We conducted comprehensive high-throughput transcriptomic analysis of pure human SAN primary pacemaker tissue and neighboring right atrial tissue from human transplanted HF hearts (n = 10) and non-failing (nHF) donor hearts (n = 9), using next-generation sequencing. Overall, 47 miRs and 832 mRNAs related to multiple signaling pathways, including cardiac diseases, tachy-brady arrhythmias and fibrosis, were significantly altered in HF SAN. Of the altered miRs, 27 are predicted to regulate mRNAs of major ion channels and neurotransmitter receptors which are involved in SAN automaticity (e.g. HCN1, HCN4, SLC8A1) and intranodal conduction (e.g. SCN5A, SCN8A) or both (e.g. KCNJ3, KCNJ5). Luciferase reporter assays were used to validate interactions of miRs with predicted mRNA targets. In conclusion, our study provides a profile of altered miRs in HF human SAN, and a novel transcriptome blueprint to identify molecular targets for SAN dysfunction and arrhythmia treatments in HF.Ning LiEsthela ArtigaAnuradha KalyanasundaramBrian J. HansenAmy WebbMaciej PietrzakBrandon BiesiadeckiBryan WhitsonNahush A. MokadamPaul M. L. JanssenJohn D. HummelPeter J. MohlerHalina DobrzynskiVadim V. FedorovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ning Li Esthela Artiga Anuradha Kalyanasundaram Brian J. Hansen Amy Webb Maciej Pietrzak Brandon Biesiadecki Bryan Whitson Nahush A. Mokadam Paul M. L. Janssen John D. Hummel Peter J. Mohler Halina Dobrzynski Vadim V. Fedorov Altered microRNA and mRNA profiles during heart failure in the human sinoatrial node
description	Abstract Heart failure (HF) is frequently accompanied with the sinoatrial node (SAN) dysfunction, which causes tachy-brady arrhythmias and increased mortality. MicroRNA (miR) alterations are associated with HF progression. However, the transcriptome of HF human SAN, and its role in HF-associated remodeling of ion channels, transporters, and receptors responsible for SAN automaticity and conduction impairments is unknown. We conducted comprehensive high-throughput transcriptomic analysis of pure human SAN primary pacemaker tissue and neighboring right atrial tissue from human transplanted HF hearts (n = 10) and non-failing (nHF) donor hearts (n = 9), using next-generation sequencing. Overall, 47 miRs and 832 mRNAs related to multiple signaling pathways, including cardiac diseases, tachy-brady arrhythmias and fibrosis, were significantly altered in HF SAN. Of the altered miRs, 27 are predicted to regulate mRNAs of major ion channels and neurotransmitter receptors which are involved in SAN automaticity (e.g. HCN1, HCN4, SLC8A1) and intranodal conduction (e.g. SCN5A, SCN8A) or both (e.g. KCNJ3, KCNJ5). Luciferase reporter assays were used to validate interactions of miRs with predicted mRNA targets. In conclusion, our study provides a profile of altered miRs in HF human SAN, and a novel transcriptome blueprint to identify molecular targets for SAN dysfunction and arrhythmia treatments in HF.
format	article
author	Ning Li Esthela Artiga Anuradha Kalyanasundaram Brian J. Hansen Amy Webb Maciej Pietrzak Brandon Biesiadecki Bryan Whitson Nahush A. Mokadam Paul M. L. Janssen John D. Hummel Peter J. Mohler Halina Dobrzynski Vadim V. Fedorov
author_facet	Ning Li Esthela Artiga Anuradha Kalyanasundaram Brian J. Hansen Amy Webb Maciej Pietrzak Brandon Biesiadecki Bryan Whitson Nahush A. Mokadam Paul M. L. Janssen John D. Hummel Peter J. Mohler Halina Dobrzynski Vadim V. Fedorov
author_sort	Ning Li
title	Altered microRNA and mRNA profiles during heart failure in the human sinoatrial node
title_short	Altered microRNA and mRNA profiles during heart failure in the human sinoatrial node
title_full	Altered microRNA and mRNA profiles during heart failure in the human sinoatrial node
title_fullStr	Altered microRNA and mRNA profiles during heart failure in the human sinoatrial node
title_full_unstemmed	Altered microRNA and mRNA profiles during heart failure in the human sinoatrial node
title_sort	altered microrna and mrna profiles during heart failure in the human sinoatrial node
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d1f3400a06c3430697951538c406b0ec
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Altered microRNA and mRNA profiles during heart failure in the human sinoatrial node

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