Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction

Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction

Abstract Heart failure with reduced ejection fraction (HFrEF) constitutes 50% of HF hospitalizations and is characterized by high rates of mortality. To explore the underlying mechanisms of HFrEF etiology and progression, we studied the molecular and cellular differences in four chambers of non-fail...

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Autores principales: Xin Luo, Jun Yin, Denise Dwyer, Tracy Yamawaki, Hong Zhou, Hongfei Ge, Chun-Ya Han, Artem Shkumatov, Karen Snyder, Brandon Ason, Chi-Ming Li, Oliver Homann, Marina Stolina
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Science
Q
Acceso en línea:https://doaj.org/article/633f57b6f6c4436da829a83c32e7490b
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spelling oai:doaj.org-article:633f57b6f6c4436da829a83c32e7490b2021-12-02T17:50:56ZChamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction10.1038/s41598-021-91214-22045-2322https://doaj.org/article/633f57b6f6c4436da829a83c32e7490b2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91214-2https://doaj.org/toc/2045-2322Abstract Heart failure with reduced ejection fraction (HFrEF) constitutes 50% of HF hospitalizations and is characterized by high rates of mortality. To explore the underlying mechanisms of HFrEF etiology and progression, we studied the molecular and cellular differences in four chambers of non-failing (NF, n = 10) and HFrEF (n = 12) human hearts. We identified 333 genes enriched within NF heart subregions and often associated with cardiovascular disease GWAS variants. Expression analysis of HFrEF tissues revealed extensive disease-associated transcriptional and signaling alterations in left atrium (LA) and left ventricle (LV). Common left heart HFrEF pathologies included mitochondrial dysfunction, cardiac hypertrophy and fibrosis. Oxidative stress and cardiac necrosis pathways were prominent within LV, whereas TGF-beta signaling was evident within LA. Cell type composition was estimated by deconvolution and revealed that HFrEF samples had smaller percentage of cardiomyocytes within the left heart, higher representation of fibroblasts within LA and perivascular cells within the left heart relative to NF samples. We identified essential modules associated with HFrEF pathology and linked transcriptome discoveries with human genetics findings. This study contributes to a growing body of knowledge describing chamber-specific transcriptomics and revealed genes and pathways that are associated with heart failure pathophysiology, which may aid in therapeutic target discovery.Xin LuoJun YinDenise DwyerTracy YamawakiHong ZhouHongfei GeChun-Ya HanArtem ShkumatovKaren SnyderBrandon AsonChi-Ming LiOliver HomannMarina StolinaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Xin Luo
Jun Yin
Denise Dwyer
Tracy Yamawaki
Hong Zhou
Hongfei Ge
Chun-Ya Han
Artem Shkumatov
Karen Snyder
Brandon Ason
Chi-Ming Li
Oliver Homann
Marina Stolina
Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction
description Abstract Heart failure with reduced ejection fraction (HFrEF) constitutes 50% of HF hospitalizations and is characterized by high rates of mortality. To explore the underlying mechanisms of HFrEF etiology and progression, we studied the molecular and cellular differences in four chambers of non-failing (NF, n = 10) and HFrEF (n = 12) human hearts. We identified 333 genes enriched within NF heart subregions and often associated with cardiovascular disease GWAS variants. Expression analysis of HFrEF tissues revealed extensive disease-associated transcriptional and signaling alterations in left atrium (LA) and left ventricle (LV). Common left heart HFrEF pathologies included mitochondrial dysfunction, cardiac hypertrophy and fibrosis. Oxidative stress and cardiac necrosis pathways were prominent within LV, whereas TGF-beta signaling was evident within LA. Cell type composition was estimated by deconvolution and revealed that HFrEF samples had smaller percentage of cardiomyocytes within the left heart, higher representation of fibroblasts within LA and perivascular cells within the left heart relative to NF samples. We identified essential modules associated with HFrEF pathology and linked transcriptome discoveries with human genetics findings. This study contributes to a growing body of knowledge describing chamber-specific transcriptomics and revealed genes and pathways that are associated with heart failure pathophysiology, which may aid in therapeutic target discovery.
format article
author Xin Luo
Jun Yin
Denise Dwyer
Tracy Yamawaki
Hong Zhou
Hongfei Ge
Chun-Ya Han
Artem Shkumatov
Karen Snyder
Brandon Ason
Chi-Ming Li
Oliver Homann
Marina Stolina
author_facet Xin Luo
Jun Yin
Denise Dwyer
Tracy Yamawaki
Hong Zhou
Hongfei Ge
Chun-Ya Han
Artem Shkumatov
Karen Snyder
Brandon Ason
Chi-Ming Li
Oliver Homann
Marina Stolina
author_sort Xin Luo
title Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction
title_short Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction
title_full Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction
title_fullStr Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction
title_full_unstemmed Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction
title_sort chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/633f57b6f6c4436da829a83c32e7490b
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