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Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling

Elevated cis-epoxyeicosatrienoic acids (EETs) are known to be cardioprotective during ischemia-reperfusion injury in cardiomyocyte-specific overexpressing cytochrome P450 2J2 (CYP2J2) transgenic (Tr) mice. Using the same Tr mice, we measured changes in cardiac and erythrocyte membranes EETs followin...

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Autores principales: Aliwarga, Theresa, Guo, Xiaoyun, Evangelista, Eric A., Lemaitre, Rozenn N., Sotoodehnia, Nona, Gharib, Sina A., Zeldin, Darryl C., Liu, Qinghang, Totah, Rheem A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344501/
https://www.ncbi.nlm.nih.gov/pubmed/32486275
http://dx.doi.org/10.3390/biomedicines8060144
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author Aliwarga, Theresa
Guo, Xiaoyun
Evangelista, Eric A.
Lemaitre, Rozenn N.
Sotoodehnia, Nona
Gharib, Sina A.
Zeldin, Darryl C.
Liu, Qinghang
Totah, Rheem A.
author_facet Aliwarga, Theresa
Guo, Xiaoyun
Evangelista, Eric A.
Lemaitre, Rozenn N.
Sotoodehnia, Nona
Gharib, Sina A.
Zeldin, Darryl C.
Liu, Qinghang
Totah, Rheem A.
author_sort Aliwarga, Theresa
collection PubMed
description Elevated cis-epoxyeicosatrienoic acids (EETs) are known to be cardioprotective during ischemia-reperfusion injury in cardiomyocyte-specific overexpressing cytochrome P450 2J2 (CYP2J2) transgenic (Tr) mice. Using the same Tr mice, we measured changes in cardiac and erythrocyte membranes EETs following myocardial infarction (MI) to determine if they can serve as reporters for cardiac events. Cardiac function was also assessed in Tr vs. wild-type (WT) mice in correlation with EET changes two weeks following MI. Tr mice (N = 25, 16 female, nine male) had significantly higher cardiac cis- and trans-EETs compared to their WT counterparts (N = 25, 18 female, seven male). Total cardiac cis-EETs in Tr mice were positively correlated with total cis-EETs in erythrocyte membrane, but there was no correlation with trans-EETs or in WT mice. Following MI, cis- and trans-EETs were elevated in the erythrocyte membrane and cardiac tissue in Tr mice, accounting for the improved cardiac outcomes observed. Tr mice showed significantly better myocardial remodeling following MI, evidenced by higher % fractional shortening, smaller infarct size, lower reactive oxygen species (ROS) formation, reduced fibrosis and apoptosis, and lower pulmonary edema. A positive correlation between total cardiac cis-EETs and total erythrocyte membrane cis-EETs in a Tr mouse model suggests that erythrocyte cis-EETs may be used as predictive markers for cardiac events. All cis-EET regioisomers displayed similar trends following acute MI; however, the magnitude of change for each regioisomer was markedly different, warranting measurement of each individually.
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spelling pubmed-73445012020-07-14 Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling Aliwarga, Theresa Guo, Xiaoyun Evangelista, Eric A. Lemaitre, Rozenn N. Sotoodehnia, Nona Gharib, Sina A. Zeldin, Darryl C. Liu, Qinghang Totah, Rheem A. Biomedicines Article Elevated cis-epoxyeicosatrienoic acids (EETs) are known to be cardioprotective during ischemia-reperfusion injury in cardiomyocyte-specific overexpressing cytochrome P450 2J2 (CYP2J2) transgenic (Tr) mice. Using the same Tr mice, we measured changes in cardiac and erythrocyte membranes EETs following myocardial infarction (MI) to determine if they can serve as reporters for cardiac events. Cardiac function was also assessed in Tr vs. wild-type (WT) mice in correlation with EET changes two weeks following MI. Tr mice (N = 25, 16 female, nine male) had significantly higher cardiac cis- and trans-EETs compared to their WT counterparts (N = 25, 18 female, seven male). Total cardiac cis-EETs in Tr mice were positively correlated with total cis-EETs in erythrocyte membrane, but there was no correlation with trans-EETs or in WT mice. Following MI, cis- and trans-EETs were elevated in the erythrocyte membrane and cardiac tissue in Tr mice, accounting for the improved cardiac outcomes observed. Tr mice showed significantly better myocardial remodeling following MI, evidenced by higher % fractional shortening, smaller infarct size, lower reactive oxygen species (ROS) formation, reduced fibrosis and apoptosis, and lower pulmonary edema. A positive correlation between total cardiac cis-EETs and total erythrocyte membrane cis-EETs in a Tr mouse model suggests that erythrocyte cis-EETs may be used as predictive markers for cardiac events. All cis-EET regioisomers displayed similar trends following acute MI; however, the magnitude of change for each regioisomer was markedly different, warranting measurement of each individually. MDPI 2020-05-30 /pmc/articles/PMC7344501/ /pubmed/32486275 http://dx.doi.org/10.3390/biomedicines8060144 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aliwarga, Theresa
Guo, Xiaoyun
Evangelista, Eric A.
Lemaitre, Rozenn N.
Sotoodehnia, Nona
Gharib, Sina A.
Zeldin, Darryl C.
Liu, Qinghang
Totah, Rheem A.
Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling
title Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling
title_full Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling
title_fullStr Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling
title_full_unstemmed Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling
title_short Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling
title_sort higher epoxyeicosatrienoic acids in cardiomyocytes-specific cyp2j2 transgenic mice are associated with improved myocardial remodeling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344501/
https://www.ncbi.nlm.nih.gov/pubmed/32486275
http://dx.doi.org/10.3390/biomedicines8060144
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