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 language | English (US) |
|---|---|
| Pages (from-to) | 835-845 |
| Number of pages | 11 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 47 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2009 |
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Keywords
- Epoxyeicosatrienoic acids
- Myocardial infarction
- Oxylipin profiling
- Soluble epoxide hydrolase
- Soluble epoxide hydrolase inhibitors
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine
Cite this
Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model : Insight gained using metabolomic approaches. / Li, Ning; Liu, Jun Yan; Timofeyev, Valeriy; Qiu, Hong; Hwang, Sung Hee; Tuteja, Dipika; Lu, Ling; Yang, Jun; Mochida, Hideki; Low, Reginald; Hammock, Bruce D.; Chiamvimonvat, Nipavan.
In: Journal of Molecular and Cellular Cardiology, Vol. 47, No. 6, 12.2009, p. 835-845.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model
T2 - Insight gained using metabolomic approaches
AU - Li, Ning
AU - Liu, Jun Yan
AU - Timofeyev, Valeriy
AU - Qiu, Hong
AU - Hwang, Sung Hee
AU - Tuteja, Dipika
AU - Lu, Ling
AU - Yang, Jun
AU - Mochida, Hideki
AU - Low, Reginald
AU - Hammock, Bruce D.
AU - Chiamvimonvat, Nipavan
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - Epoxyeicosatrienoic acids
KW - Myocardial infarction
KW - Oxylipin profiling
KW - Soluble epoxide hydrolase
KW - Soluble epoxide hydrolase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=70350604449&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350604449&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2009.08.017
DO - 10.1016/j.yjmcc.2009.08.017
M3 - Article
C2 - 19716829
AN - SCOPUS:70350604449
VL - 47
SP - 835
EP - 845
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 6
ER -