CYP-450 Epoxygenase Derived Epoxyeicosatrienoic Acid Contribute To Reversal of Heart Failure in Obesity-Induced Diabetic Cardiomyopathy via PGC-1 alpha Activation

Authors

Shailendra Singh, New York Medical CollegeFollow
John A. McClung, New York Medical CollegeFollow
Lars Bellner, New York Medical CollegeFollow
Jian Cao
Maayan Waldman
Joseph Schragenheim, New York Medical College
Nader G. Abraham, New York Medical CollegeFollow

Journal Title

Cardiovascular Pharmacology: Open Access

First Page

233

Document Type

Article

Publication Date

2-1-2018

Department

Medicine

Abstract

We have previously shown that an Epoxyeicosatrienoic Acid (EET) -agonist has pleiotropic effects and reverses cardiomyopathy by decreasing inflammatory molecules and increasing antioxidant signaling. We hypothesized that administration of an EET agonist would increase Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha), which controls mitochondrial function and induction of HO-1 and negatively regulates the expression of the proinflammatory adipokines CCN3/NOV in cardiac and pericardial tissues. This pathway would be expected to further improve left ventricular (LV) systolic function as well as increase insulin receptor phosphorylation. Measurement of the effect of an EET agonist on oxygen consumption, fractional shortening, blood glucose levels, thermogenic and mitochondrial signaling proteins was performed. Control obese mice developed signs of metabolic syndrome including insulin resistance, hypertension, inflammation, LV dysfunction, and increased NOV expression in pericardial adipose tissue. EET agonist intervention decreased pericardial adipose tissue expression of NOV, while normalized FS, increased PGC-1alpha, HO-1 levels, insulin receptor phosphorylation and improved mitochondrial function, theses beneficial effect were reversed by deletion of PGC-1alpha. These studies demonstrate that an EET agonist increases insulin receptor phosphorylation, mitochondrial and thermogenic gene expression, decreased cardiac and pericardial tissue NOV levels, and ameliorates cardiomyopathy in an obese mouse model of the metabolic syndrome.

Comments

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Recommended Citation

Singh, S., McClung, J., Bellner, L., Cao, J., Waldman, M., Schragenheim, J., & Abraham, N. (2018). CYP-450 Epoxygenase Derived Epoxyeicosatrienoic Acid Contribute To Reversal of Heart Failure in Obesity-Induced Diabetic Cardiomyopathy via PGC-1 alpha Activation. Cardiovascular Pharmacology: Open Access, 7 (1), 233. https://doi.org/10.4172/2329-6607.1000233

Publisher's Statement

Originally published in Cardiovascular Pharmacology: Open Access, 7(1) [Article 1000233]. The original material can be found here.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.