Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches

Ning Li, Jun Yan Liu, Valeriy Timofeyev, Hong Qiu, Sung Hee Hwang, Dipika Tuteja, Ling Lu, Jun Yang, Hideki Mochida, Reginald Low, Bruce D. Hammock, Nipavan Chiamvimonvat

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Myocardial infarction (MI) leading to myocardial cell loss represents one of the common causes leading to cardiac failure. We have previously demonstrated the beneficial effects of several potent soluble epoxide hydrolase (sEH) inhibitors in cardiac hypertrophy. sEH catalizes the conversion of epoxyeicosatrienoic acids (EETs) to form the corresponding dihydroxyeicosatrienoic acids (DHETs). EETs are products of cytochrome P450 epoxygenases that have vasodilatory properties. Additionally, EETs inhibit the activation of nuclear factor (NF)-κB-mediated gene transcription. Motivated by the potential to uncover a new class of therapeutic agents for cardiovascular diseases which can be effectively used in clinical setting, we directly tested the biological effects of sEH inhibitors (sEHIs) on the progression of cardiac remodeling using a clinically relevant murine model of MI. We demonstrated that sEHIs were highly effective in the prevention of progressive cardiac remodeling post MI. Using metabolomic profiling of the inflammatory lipid mediators, we documented a significant decrease in EETs/DHETs ratio in MI model predicting a heightened inflammatory state. Treatment with sEHIs resulted in a change in the pattern of lipid mediators from one of inflammation towards resolution. Moreover, the oxylipin profiling showed a striking parallel to the changes in inflammatory cytokines in this model. Our study provides evidence for a possible new therapeutic strategy to improve cardiac function post MI.

Original languageEnglish (US)
Pages (from-to)835-845
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume47
Issue number6
DOIs
StatePublished - Dec 2009

Keywords

  • Epoxyeicosatrienoic acids
  • Myocardial infarction
  • Oxylipin profiling
  • Soluble epoxide hydrolase
  • Soluble epoxide hydrolase inhibitors

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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