Soluble epoxide hydrolase inhibition exerts beneficial anti-remodeling actions post-myocardial infarction

AR Kompa; BH Wang; G Xu; Y Zhang; PY Ho; S Eisennagel; RK Thalji; JP Marino; DJ Kelly; DJ Behm; H Krum

Journal article

Soluble epoxide hydrolase inhibition exerts beneficial anti-remodeling actions post-myocardial infarction

AR Kompa, BH Wang, G Xu, Y Zhang, PY Ho, S Eisennagel, RK Thalji, JP Marino, DJ Kelly, DJ Behm, H Krum

International Journal of Cardiology | Published : 2013

DOI: 10.1016/j.ijcard.2011.12.062

Abstract

Background: A contributory role for soluble epoxide hydrolase (sEH) in cardiac remodeling post-myocardial infarction (MI) has been suggested; however effects of sEH inhibition following MI have not been evaluated. In this study, we examined in vivo post-MI anti-remodeling effects of a novel sEH inhibitor (GSK2188931B) in the rat, and evaluated its direct in vitro effects on hypertrophy, fibrosis and inflammation. Methods and results: Post-MI administered GSK2188931B (80 mg/kg/d in chow) for 5 weeks improved left ventricular (LV) ejection fraction compared to vehicle-treated (Veh) rats (P < 0.01; Sham 65 ± 2%, MI + Veh 30 ± 2%, MI + GSK 43 ± 2%) without affecting systolic blood pressure. Perc..

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University of Melbourne Researchers

Andrew Kompa Author

Darren Kelly Author

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Grants

Awarded by GlaxoSmithKline

Funding Acknowledgements

This study was supported by GlaxoSmithKline and the National Health and Medical Research Council of Australia grants [334008] and [546272]. The authors would like to thank Ms Mariana Pacheco and Ms Jemma Court for technical support with the animal studies. "The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology."