Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease

Abstract The study examines the whole blood transcriptome profile before and after cardiopulmonary bypass (CPB) in neonates with hypoplastic left heart syndrome (HLHS), a severe form of congenital heart disease, that can develop low cardiac output syndrome (LCOS). Whole blood mRNA transcriptome prof...

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Autores principales:	Parag N. Jain, Matthew Robertson, Javier J. Lasa, Lara Shekerdemian, Danielle Guffey, Yuhao Zhang, Krithika Lingappan, Paul Checchia, Cristian Coarfa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fbdabfac3e974381be86352f0fae6c19
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spelling	oai:doaj.org-article:fbdabfac3e974381be86352f0fae6c192021-12-02T13:20:20ZAltered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease10.1038/s41598-021-83882-x2045-2322https://doaj.org/article/fbdabfac3e974381be86352f0fae6c192021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83882-xhttps://doaj.org/toc/2045-2322Abstract The study examines the whole blood transcriptome profile before and after cardiopulmonary bypass (CPB) in neonates with hypoplastic left heart syndrome (HLHS), a severe form of congenital heart disease, that can develop low cardiac output syndrome (LCOS). Whole blood mRNA transcriptome profiles of 13 neonates with HLHS before and after their first palliative surgery were analyzed to determine differentially expressed genes and pathways. The median age and weight at surgery were 4 days and 3.2 kg, respectively. Of the 13 patients, 8 developed LCOS. There was no significant difference between CPB, aortic cross clamp, deep hypothermic cardiac arrest times between patients that develop LCOS and those that do not. Upon comparing differential gene expression profiles between patients that develop LCOS and those that do not in pre-operative samples, 1 gene was up-regulated and 13 were down regulated. In the post-operative samples, 4 genes were up-regulated, and 4 genes were down regulated when patients that develop LCOS were compared to those that do not. When comparing post-operative samples to pre-operative samples in the patients that do not develop LCOS, 1484 genes were up-regulated, and 1388 genes were down regulated; while patients that developed LCOS had 2423 up-regulated genes, and 2414 down regulated genes for the same pre to post-operative comparison. Pathway analysis revealed differential regulation of inflammatory pathways (IL signaling, PDGF, NOTCH1, NGF, GPCR) and metabolic pathways (heme metabolism, oxidative phosphorylation, protein metabolism including amino acid and derivatives, fatty acid metabolism, TCA cycle and respiratory electron transport chain). By identifying altered transcriptome profiles related to inflammation and metabolism in neonates with HLHS who develop LCOS after CPB, this study opens for exploration novel pathways and potential therapeutic targets to improve outcomes in this high-risk population.Parag N. JainMatthew RobertsonJavier J. LasaLara ShekerdemianDanielle GuffeyYuhao ZhangKrithika LingappanPaul ChecchiaCristian CoarfaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Parag N. Jain Matthew Robertson Javier J. Lasa Lara Shekerdemian Danielle Guffey Yuhao Zhang Krithika Lingappan Paul Checchia Cristian Coarfa Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease
description	Abstract The study examines the whole blood transcriptome profile before and after cardiopulmonary bypass (CPB) in neonates with hypoplastic left heart syndrome (HLHS), a severe form of congenital heart disease, that can develop low cardiac output syndrome (LCOS). Whole blood mRNA transcriptome profiles of 13 neonates with HLHS before and after their first palliative surgery were analyzed to determine differentially expressed genes and pathways. The median age and weight at surgery were 4 days and 3.2 kg, respectively. Of the 13 patients, 8 developed LCOS. There was no significant difference between CPB, aortic cross clamp, deep hypothermic cardiac arrest times between patients that develop LCOS and those that do not. Upon comparing differential gene expression profiles between patients that develop LCOS and those that do not in pre-operative samples, 1 gene was up-regulated and 13 were down regulated. In the post-operative samples, 4 genes were up-regulated, and 4 genes were down regulated when patients that develop LCOS were compared to those that do not. When comparing post-operative samples to pre-operative samples in the patients that do not develop LCOS, 1484 genes were up-regulated, and 1388 genes were down regulated; while patients that developed LCOS had 2423 up-regulated genes, and 2414 down regulated genes for the same pre to post-operative comparison. Pathway analysis revealed differential regulation of inflammatory pathways (IL signaling, PDGF, NOTCH1, NGF, GPCR) and metabolic pathways (heme metabolism, oxidative phosphorylation, protein metabolism including amino acid and derivatives, fatty acid metabolism, TCA cycle and respiratory electron transport chain). By identifying altered transcriptome profiles related to inflammation and metabolism in neonates with HLHS who develop LCOS after CPB, this study opens for exploration novel pathways and potential therapeutic targets to improve outcomes in this high-risk population.
format	article
author	Parag N. Jain Matthew Robertson Javier J. Lasa Lara Shekerdemian Danielle Guffey Yuhao Zhang Krithika Lingappan Paul Checchia Cristian Coarfa
author_facet	Parag N. Jain Matthew Robertson Javier J. Lasa Lara Shekerdemian Danielle Guffey Yuhao Zhang Krithika Lingappan Paul Checchia Cristian Coarfa
author_sort	Parag N. Jain
title	Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease
title_short	Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease
title_full	Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease
title_fullStr	Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease
title_full_unstemmed	Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease
title_sort	altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fbdabfac3e974381be86352f0fae6c19
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Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease

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