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Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia

Chronic hypoxia from diseases in the lung, such as pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease, can increase pulmonary vascular resistance, resulting in hypertrophy and dysfunction of the right ventricle (RV). In order to obtain insight into RV biology and p...

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Autores principales: Gorr, Matthew W., Sriram, Krishna, Chinn, Amy M., Muthusamy, Abinaya, Insel, Paul A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971333/
https://www.ncbi.nlm.nih.gov/pubmed/31960631
http://dx.doi.org/10.14814/phy2.14344
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author Gorr, Matthew W.
Sriram, Krishna
Chinn, Amy M.
Muthusamy, Abinaya
Insel, Paul A.
author_facet Gorr, Matthew W.
Sriram, Krishna
Chinn, Amy M.
Muthusamy, Abinaya
Insel, Paul A.
author_sort Gorr, Matthew W.
collection PubMed
description Chronic hypoxia from diseases in the lung, such as pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease, can increase pulmonary vascular resistance, resulting in hypertrophy and dysfunction of the right ventricle (RV). In order to obtain insight into RV biology and perhaps uncover potentially novel therapeutic approaches for RV dysfunction, we performed RNA‐sequencing (RNA‐seq) of RV and LV tissue from rats in normal ambient conditions or subjected to hypoxia (10% O(2)) for 2 weeks. Gene ontology and pathway analysis of the RV and LV revealed multiple transcriptomic differences, in particular increased expression in the RV of genes related to immune function in both normoxia and hypoxia. Immune cell profiling by flow cytometry of cardiac digests revealed that in both conditions, the RV had a larger percentage than the LV of double‐positive CD45(+)/CD11b/c(+) cells (which are predominantly macrophages and dendritic cells). Analysis of gene expression changes under hypoxic conditions identified multiple pathways that may contribute to hypoxia‐induced changes in the RV, including increased expression of genes related to cell mitosis/proliferation and decreased expression of genes related to metabolic processes. Together, the findings indicate that the RV differs from the LV with respect to content of immune cells and expression of certain genes, thus suggesting the two ventricles differ in aspects of pathophysiology and in potential therapeutic targets for RV dysfunction.
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spelling pubmed-69713332020-01-27 Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia Gorr, Matthew W. Sriram, Krishna Chinn, Amy M. Muthusamy, Abinaya Insel, Paul A. Physiol Rep Original Research Chronic hypoxia from diseases in the lung, such as pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease, can increase pulmonary vascular resistance, resulting in hypertrophy and dysfunction of the right ventricle (RV). In order to obtain insight into RV biology and perhaps uncover potentially novel therapeutic approaches for RV dysfunction, we performed RNA‐sequencing (RNA‐seq) of RV and LV tissue from rats in normal ambient conditions or subjected to hypoxia (10% O(2)) for 2 weeks. Gene ontology and pathway analysis of the RV and LV revealed multiple transcriptomic differences, in particular increased expression in the RV of genes related to immune function in both normoxia and hypoxia. Immune cell profiling by flow cytometry of cardiac digests revealed that in both conditions, the RV had a larger percentage than the LV of double‐positive CD45(+)/CD11b/c(+) cells (which are predominantly macrophages and dendritic cells). Analysis of gene expression changes under hypoxic conditions identified multiple pathways that may contribute to hypoxia‐induced changes in the RV, including increased expression of genes related to cell mitosis/proliferation and decreased expression of genes related to metabolic processes. Together, the findings indicate that the RV differs from the LV with respect to content of immune cells and expression of certain genes, thus suggesting the two ventricles differ in aspects of pathophysiology and in potential therapeutic targets for RV dysfunction. John Wiley and Sons Inc. 2020-01-20 /pmc/articles/PMC6971333/ /pubmed/31960631 http://dx.doi.org/10.14814/phy2.14344 Text en © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Gorr, Matthew W.
Sriram, Krishna
Chinn, Amy M.
Muthusamy, Abinaya
Insel, Paul A.
Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia
title Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia
title_full Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia
title_fullStr Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia
title_full_unstemmed Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia
title_short Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia
title_sort transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971333/
https://www.ncbi.nlm.nih.gov/pubmed/31960631
http://dx.doi.org/10.14814/phy2.14344
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