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

1
Department of Medicinal Chemistry, University of Washington, Box 357610, Seattle, WA 98195, USA
2
Department of Physiology and Biophysics, University of Washington, Box 357290, Seattle, WA 98195, USA
3
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA
4
Division of Cardiology, University of Washington, Box 356422, Seattle, WA 98195, USA
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Computational Medicinal Core, Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, S376-815 Mercer, Box 385052, Seattle, WA 98109, USA
6
National Institute of Environmental Health Sciences, A214 Rall Building, 111 T W Alexander Dr, Research Triangle Park, NC 27709, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomedicines 2020, 8(6), 144; https://doi.org/10.3390/biomedicines8060144
Received: 28 April 2020 / Revised: 27 May 2020 / Accepted: 27 May 2020 / Published: 30 May 2020
(This article belongs to the Special Issue microRNAs as Biomarkers of Cardiovascular Diseases)
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. View Full-Text
Keywords: epoxyeicosatrienoic acids; myocardial remodeling; CYP2J2 epoxyeicosatrienoic acids; myocardial remodeling; CYP2J2
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Aliwarga, T.; Guo, X.; Evangelista, E.A.; Lemaitre, R.N.; Sotoodehnia, N.; Gharib, S.A.; Zeldin, D.C.; Liu, Q.; Totah, R.A. Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling. Biomedicines 2020, 8, 144.

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