Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome

Background: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late an...

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Autores principales:	Severi Mulari, Arda Eskin, Milla Lampinen, Annu Nummi, Tuomo Nieminen, Kari Teittinen, Teija Ojala, Matti Kankainen, Antti Vento, Jari Laurikka, Markku Kupari, Ari Harjula, Nurcan Tuncbag, Esko Kankuri
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	biomarkers ischemia chronic ischemic heart disease cardiovascular surgery atrial appendage differentially expressed genes Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/e5a77ca58bb24552a5fdc0c04e5ca02e
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spelling	oai:doaj.org-article:e5a77ca58bb24552a5fdc0c04e5ca02e2021-12-02T07:53:04ZIschemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome2297-055X10.3389/fcvm.2021.728198https://doaj.org/article/e5a77ca58bb24552a5fdc0c04e5ca02e2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.728198/fullhttps://doaj.org/toc/2297-055XBackground: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes.Methods and Results: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against 429 donors from the GTEx project without cardiac disease. The IHD transcriptome was characterized by repressed RNA expression in pathways for cell–cell contacts and mitochondrial dysfunction. Increased expressions of the CSRNP3, FUT10, SHD, NAV2-AS4, and hsa-mir-181 genes resulted in significance with the complexity of coronary artery obstructions or correlated with a functional cardiac benefit from bypass surgery.Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes characterized here, pave the way for future disease mechanism-based identification of biomarkers for early detection and treatment of IHD.Severi MulariSeveri MulariArda EskinMilla LampinenMilla LampinenAnnu NummiTuomo NieminenKari TeittinenTeija OjalaMatti KankainenAntti VentoJari LaurikkaJari LaurikkaMarkku KupariAri HarjulaNurcan TuncbagNurcan TuncbagNurcan TuncbagEsko KankuriFrontiers Media S.A.articlebiomarkersischemiachronic ischemic heart diseasecardiovascular surgeryatrial appendagedifferentially expressed genesDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	biomarkers ischemia chronic ischemic heart disease cardiovascular surgery atrial appendage differentially expressed genes Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	biomarkers ischemia chronic ischemic heart disease cardiovascular surgery atrial appendage differentially expressed genes Diseases of the circulatory (Cardiovascular) system RC666-701 Severi Mulari Severi Mulari Arda Eskin Milla Lampinen Milla Lampinen Annu Nummi Tuomo Nieminen Kari Teittinen Teija Ojala Matti Kankainen Antti Vento Jari Laurikka Jari Laurikka Markku Kupari Ari Harjula Nurcan Tuncbag Nurcan Tuncbag Nurcan Tuncbag Esko Kankuri Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome
description	Background: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes.Methods and Results: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against 429 donors from the GTEx project without cardiac disease. The IHD transcriptome was characterized by repressed RNA expression in pathways for cell–cell contacts and mitochondrial dysfunction. Increased expressions of the CSRNP3, FUT10, SHD, NAV2-AS4, and hsa-mir-181 genes resulted in significance with the complexity of coronary artery obstructions or correlated with a functional cardiac benefit from bypass surgery.Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes characterized here, pave the way for future disease mechanism-based identification of biomarkers for early detection and treatment of IHD.
format	article
author	Severi Mulari Severi Mulari Arda Eskin Milla Lampinen Milla Lampinen Annu Nummi Tuomo Nieminen Kari Teittinen Teija Ojala Matti Kankainen Antti Vento Jari Laurikka Jari Laurikka Markku Kupari Ari Harjula Nurcan Tuncbag Nurcan Tuncbag Nurcan Tuncbag Esko Kankuri
author_facet	Severi Mulari Severi Mulari Arda Eskin Milla Lampinen Milla Lampinen Annu Nummi Tuomo Nieminen Kari Teittinen Teija Ojala Matti Kankainen Antti Vento Jari Laurikka Jari Laurikka Markku Kupari Ari Harjula Nurcan Tuncbag Nurcan Tuncbag Nurcan Tuncbag Esko Kankuri
author_sort	Severi Mulari
title	Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome
title_short	Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome
title_full	Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome
title_fullStr	Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome
title_full_unstemmed	Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome
title_sort	ischemic heart disease selectively modifies the right atrial appendage transcriptome
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e5a77ca58bb24552a5fdc0c04e5ca02e
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Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome

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