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CYP2J2 Modulates Diverse Transcriptional Programs in Adult Human Cardiomyocytes
CYP2J2, a member of the Cytochrome P450 family of enzymes, is the most abundant epoxygenase in the heart and has multifunctional properties including bioactivation of arachidonic acid to epoxyeicosatrienoic acids, which, in turn, have been implicated in mediating several cardiovascular conditions. U...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093536/ https://www.ncbi.nlm.nih.gov/pubmed/32210298 http://dx.doi.org/10.1038/s41598-020-62174-w |
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author | Evangelista, Eric A. Aliwarga, Theresa Sotoodehnia, Nona Jensen, Paul N. McKnight, Barbara Lemaitre, Rozenn N. Totah, Rheem A. Gharib, Sina A. |
author_facet | Evangelista, Eric A. Aliwarga, Theresa Sotoodehnia, Nona Jensen, Paul N. McKnight, Barbara Lemaitre, Rozenn N. Totah, Rheem A. Gharib, Sina A. |
author_sort | Evangelista, Eric A. |
collection | PubMed |
description | CYP2J2, a member of the Cytochrome P450 family of enzymes, is the most abundant epoxygenase in the heart and has multifunctional properties including bioactivation of arachidonic acid to epoxyeicosatrienoic acids, which, in turn, have been implicated in mediating several cardiovascular conditions. Using a proteomic approach, we found that CYP2J2 expression is lower in cardiac tissue from patients with cardiomyopathy compared to controls. In order to better elucidate the complex role played by CYP2J2 in cardiac cells, we performed targeted silencing of CYP2J2 expression in human adult ventricular cardiomyocytes and interrogated whole genome transcriptional responses. We found that knockdown of CYP2J2 elicits widespread alterations in gene expression of ventricular cardiomyocytes and leads to the activation of a diverse repertoire of programs, including those involved in ion channel signaling, development, extracellular matrix, and metabolism. Several members of the differentially up-regulated ion channel module have well-known pathogenetic roles in cardiac dysrhythmias. By leveraging causal network and upstream regulator analysis, we identified several candidate drivers of the observed transcriptional response to CYP2J2 silencing; these master regulators have been implicated in aberrant cardiac remodeling, heart failure, and myocyte injury and repair. Collectively, our study demonstrates that CYP2J2 plays a central and multifaceted role in cardiomyocyte homeostasis and provides a framework for identifying critical regulators and pathways influenced by this gene in cardiovascular health and disease. |
format | Online Article Text |
id | pubmed-7093536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70935362020-03-27 CYP2J2 Modulates Diverse Transcriptional Programs in Adult Human Cardiomyocytes Evangelista, Eric A. Aliwarga, Theresa Sotoodehnia, Nona Jensen, Paul N. McKnight, Barbara Lemaitre, Rozenn N. Totah, Rheem A. Gharib, Sina A. Sci Rep Article CYP2J2, a member of the Cytochrome P450 family of enzymes, is the most abundant epoxygenase in the heart and has multifunctional properties including bioactivation of arachidonic acid to epoxyeicosatrienoic acids, which, in turn, have been implicated in mediating several cardiovascular conditions. Using a proteomic approach, we found that CYP2J2 expression is lower in cardiac tissue from patients with cardiomyopathy compared to controls. In order to better elucidate the complex role played by CYP2J2 in cardiac cells, we performed targeted silencing of CYP2J2 expression in human adult ventricular cardiomyocytes and interrogated whole genome transcriptional responses. We found that knockdown of CYP2J2 elicits widespread alterations in gene expression of ventricular cardiomyocytes and leads to the activation of a diverse repertoire of programs, including those involved in ion channel signaling, development, extracellular matrix, and metabolism. Several members of the differentially up-regulated ion channel module have well-known pathogenetic roles in cardiac dysrhythmias. By leveraging causal network and upstream regulator analysis, we identified several candidate drivers of the observed transcriptional response to CYP2J2 silencing; these master regulators have been implicated in aberrant cardiac remodeling, heart failure, and myocyte injury and repair. Collectively, our study demonstrates that CYP2J2 plays a central and multifaceted role in cardiomyocyte homeostasis and provides a framework for identifying critical regulators and pathways influenced by this gene in cardiovascular health and disease. Nature Publishing Group UK 2020-03-24 /pmc/articles/PMC7093536/ /pubmed/32210298 http://dx.doi.org/10.1038/s41598-020-62174-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Evangelista, Eric A. Aliwarga, Theresa Sotoodehnia, Nona Jensen, Paul N. McKnight, Barbara Lemaitre, Rozenn N. Totah, Rheem A. Gharib, Sina A. CYP2J2 Modulates Diverse Transcriptional Programs in Adult Human Cardiomyocytes |
title | CYP2J2 Modulates Diverse Transcriptional Programs in Adult Human Cardiomyocytes |
title_full | CYP2J2 Modulates Diverse Transcriptional Programs in Adult Human Cardiomyocytes |
title_fullStr | CYP2J2 Modulates Diverse Transcriptional Programs in Adult Human Cardiomyocytes |
title_full_unstemmed | CYP2J2 Modulates Diverse Transcriptional Programs in Adult Human Cardiomyocytes |
title_short | CYP2J2 Modulates Diverse Transcriptional Programs in Adult Human Cardiomyocytes |
title_sort | cyp2j2 modulates diverse transcriptional programs in adult human cardiomyocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093536/ https://www.ncbi.nlm.nih.gov/pubmed/32210298 http://dx.doi.org/10.1038/s41598-020-62174-w |
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