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Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways

Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated ca...

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Autores principales: Taylor, Jude, Yeung, Anna C. Y., Ashton, Anthony, Faiz, Alen, Guryev, Victor, Fang, Bernard, Lal, Sean, Grosser, Mark, dos Remedios, Cristobal G., Braet, Filip, McLachlan, Craig S., Li, Amy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218903/
https://www.ncbi.nlm.nih.gov/pubmed/37233155
http://dx.doi.org/10.3390/jcdd10050188
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author Taylor, Jude
Yeung, Anna C. Y.
Ashton, Anthony
Faiz, Alen
Guryev, Victor
Fang, Bernard
Lal, Sean
Grosser, Mark
dos Remedios, Cristobal G.
Braet, Filip
McLachlan, Craig S.
Li, Amy
author_facet Taylor, Jude
Yeung, Anna C. Y.
Ashton, Anthony
Faiz, Alen
Guryev, Victor
Fang, Bernard
Lal, Sean
Grosser, Mark
dos Remedios, Cristobal G.
Braet, Filip
McLachlan, Craig S.
Li, Amy
author_sort Taylor, Jude
collection PubMed
description Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated cardiomyopathy (DCM). In this study, we examined two independent RNAseq datasets from the left ventricle of end-stage PPCM patients and compared gene expression profiles to female DCM and non-failing donors. Differential gene expression, enrichment analysis and cellular deconvolution were performed to identify key processes in disease pathology. PPCM and DCM display similar enrichment in metabolic pathways and extracellular matrix remodeling suggesting these are similar processes across end-stage systolic heart failure. Genes involved in golgi vesicles biogenesis and budding were enriched in PPCM left ventricles compared to healthy donors but were not found in DCM. Furthermore, changes in immune cell populations are evident in PPCM but to a lesser extent compared to DCM, where the latter is associated with pronounced pro-inflammatory and cytotoxic T cell activity. This study reveals several pathways that are common to end-stage heart failure but also identifies potential targets of disease that may be unique to PPCM and DCM.
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spelling pubmed-102189032023-05-27 Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways Taylor, Jude Yeung, Anna C. Y. Ashton, Anthony Faiz, Alen Guryev, Victor Fang, Bernard Lal, Sean Grosser, Mark dos Remedios, Cristobal G. Braet, Filip McLachlan, Craig S. Li, Amy J Cardiovasc Dev Dis Article Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated cardiomyopathy (DCM). In this study, we examined two independent RNAseq datasets from the left ventricle of end-stage PPCM patients and compared gene expression profiles to female DCM and non-failing donors. Differential gene expression, enrichment analysis and cellular deconvolution were performed to identify key processes in disease pathology. PPCM and DCM display similar enrichment in metabolic pathways and extracellular matrix remodeling suggesting these are similar processes across end-stage systolic heart failure. Genes involved in golgi vesicles biogenesis and budding were enriched in PPCM left ventricles compared to healthy donors but were not found in DCM. Furthermore, changes in immune cell populations are evident in PPCM but to a lesser extent compared to DCM, where the latter is associated with pronounced pro-inflammatory and cytotoxic T cell activity. This study reveals several pathways that are common to end-stage heart failure but also identifies potential targets of disease that may be unique to PPCM and DCM. MDPI 2023-04-23 /pmc/articles/PMC10218903/ /pubmed/37233155 http://dx.doi.org/10.3390/jcdd10050188 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Taylor, Jude
Yeung, Anna C. Y.
Ashton, Anthony
Faiz, Alen
Guryev, Victor
Fang, Bernard
Lal, Sean
Grosser, Mark
dos Remedios, Cristobal G.
Braet, Filip
McLachlan, Craig S.
Li, Amy
Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways
title Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways
title_full Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways
title_fullStr Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways
title_full_unstemmed Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways
title_short Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways
title_sort transcriptomic comparison of human peripartum and dilated cardiomyopathy identifies differences in key disease pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218903/
https://www.ncbi.nlm.nih.gov/pubmed/37233155
http://dx.doi.org/10.3390/jcdd10050188
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