A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARγ to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction

Dan Yan Xu, Benjamin B. Davis, Zhen He Wang, Shui Ping Zhao, Binaya Wasti, Zhe Liang Liu, Ning Li, Christophe Morisseau, Nipavan Chiamvimonvat, Bruce D. Hammock

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Epoxyeicosatrienoic acids (EETs) are natural angiogenic mediators regulated by soluble epoxide hydrolase (sEH). Inhibitors of sEH can stabilize EETs levels and were reported to reduce atherosclerosis and inhibit myocardial infarction in animal models. In this work, we investigated whether increasing EETs with the sEH inhibitor t-AUCB would increase angiogenesis related function in endothelial progenitor cells (EPCs) from patients with acute myocardial infarction (AMI). Methods and results: EPCs were isolated from 50 AMI patients and 50 healthy subjects (control). EPCs were treated with different concentrations of t-AUCB for 24 h with or without peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662. Migration of EPCs was assayed in trans-well chambers. Angiogenesis assays were performed using a Matrigel-Matrix in vitro model. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) mRNA and protein in EPCs was measured by real-time PCR or Western blot, respectively. Also, the concentration of EETs in the culture supernatant was detected by ELISA. The activity of EPCs in the AMI patient group was reduced compared to healthy controls. Whereas increasing EET levels with t-AUCB promoted a dose dependent angiogenesis and migration in EPCs from AMI patients. Additionally, the t-AUCB dose dependently increased the expression of the angiogenic factors VEGF and HIF-α. Lastly, we provide evidence that these effects were PPARγ dependent. Conclusion: The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs-PPARγ pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.

Original languageEnglish (US)
Pages (from-to)1298-1304
Number of pages7
JournalInternational Journal of Cardiology
Volume167
Issue number4
DOIs
StatePublished - Aug 20 2013

Fingerprint

Epoxide Hydrolases
Peroxisome Proliferator-Activated Receptors
Myocardial Infarction
Vascular Endothelial Growth Factor A
Hypoxia-Inducible Factor 1
Endothelial Progenitor Cells
4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid
Angiogenesis Inducing Agents
Myocardial Ischemia
Real-Time Polymerase Chain Reaction
Atherosclerosis
Healthy Volunteers
Animal Models
Western Blotting
Enzyme-Linked Immunosorbent Assay
Messenger RNA
Acids

Keywords

  • Acute myocardial infarction
  • Endothelial progenitor cells
  • Soluble epoxide hydrolase inhibitor
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARγ to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction. / Xu, Dan Yan; Davis, Benjamin B.; Wang, Zhen He; Zhao, Shui Ping; Wasti, Binaya; Liu, Zhe Liang; Li, Ning; Morisseau, Christophe; Chiamvimonvat, Nipavan; Hammock, Bruce D.

In: International Journal of Cardiology, Vol. 167, No. 4, 20.08.2013, p. 1298-1304.

Research output: Contribution to journalArticle

Xu, Dan Yan ; Davis, Benjamin B. ; Wang, Zhen He ; Zhao, Shui Ping ; Wasti, Binaya ; Liu, Zhe Liang ; Li, Ning ; Morisseau, Christophe ; Chiamvimonvat, Nipavan ; Hammock, Bruce D. / A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARγ to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction. In: International Journal of Cardiology. 2013 ; Vol. 167, No. 4. pp. 1298-1304.
@article{a3143d236c854156ae6c3b348cdb0368,
title = "A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARγ to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction",
abstract = "Background: Epoxyeicosatrienoic acids (EETs) are natural angiogenic mediators regulated by soluble epoxide hydrolase (sEH). Inhibitors of sEH can stabilize EETs levels and were reported to reduce atherosclerosis and inhibit myocardial infarction in animal models. In this work, we investigated whether increasing EETs with the sEH inhibitor t-AUCB would increase angiogenesis related function in endothelial progenitor cells (EPCs) from patients with acute myocardial infarction (AMI). Methods and results: EPCs were isolated from 50 AMI patients and 50 healthy subjects (control). EPCs were treated with different concentrations of t-AUCB for 24 h with or without peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662. Migration of EPCs was assayed in trans-well chambers. Angiogenesis assays were performed using a Matrigel-Matrix in vitro model. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) mRNA and protein in EPCs was measured by real-time PCR or Western blot, respectively. Also, the concentration of EETs in the culture supernatant was detected by ELISA. The activity of EPCs in the AMI patient group was reduced compared to healthy controls. Whereas increasing EET levels with t-AUCB promoted a dose dependent angiogenesis and migration in EPCs from AMI patients. Additionally, the t-AUCB dose dependently increased the expression of the angiogenic factors VEGF and HIF-α. Lastly, we provide evidence that these effects were PPARγ dependent. Conclusion: The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs-PPARγ pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.",
keywords = "Acute myocardial infarction, Endothelial progenitor cells, Soluble epoxide hydrolase inhibitor, Vascular endothelial growth factor",
author = "Xu, {Dan Yan} and Davis, {Benjamin B.} and Wang, {Zhen He} and Zhao, {Shui Ping} and Binaya Wasti and Liu, {Zhe Liang} and Ning Li and Christophe Morisseau and Nipavan Chiamvimonvat and Hammock, {Bruce D.}",
year = "2013",
month = "8",
day = "20",
doi = "10.1016/j.ijcard.2012.03.167",
language = "English (US)",
volume = "167",
pages = "1298--1304",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",
number = "4",

}

TY - JOUR

T1 - A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARγ to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction

AU - Xu, Dan Yan

AU - Davis, Benjamin B.

AU - Wang, Zhen He

AU - Zhao, Shui Ping

AU - Wasti, Binaya

AU - Liu, Zhe Liang

AU - Li, Ning

AU - Morisseau, Christophe

AU - Chiamvimonvat, Nipavan

AU - Hammock, Bruce D.

PY - 2013/8/20

Y1 - 2013/8/20

N2 - Background: Epoxyeicosatrienoic acids (EETs) are natural angiogenic mediators regulated by soluble epoxide hydrolase (sEH). Inhibitors of sEH can stabilize EETs levels and were reported to reduce atherosclerosis and inhibit myocardial infarction in animal models. In this work, we investigated whether increasing EETs with the sEH inhibitor t-AUCB would increase angiogenesis related function in endothelial progenitor cells (EPCs) from patients with acute myocardial infarction (AMI). Methods and results: EPCs were isolated from 50 AMI patients and 50 healthy subjects (control). EPCs were treated with different concentrations of t-AUCB for 24 h with or without peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662. Migration of EPCs was assayed in trans-well chambers. Angiogenesis assays were performed using a Matrigel-Matrix in vitro model. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) mRNA and protein in EPCs was measured by real-time PCR or Western blot, respectively. Also, the concentration of EETs in the culture supernatant was detected by ELISA. The activity of EPCs in the AMI patient group was reduced compared to healthy controls. Whereas increasing EET levels with t-AUCB promoted a dose dependent angiogenesis and migration in EPCs from AMI patients. Additionally, the t-AUCB dose dependently increased the expression of the angiogenic factors VEGF and HIF-α. Lastly, we provide evidence that these effects were PPARγ dependent. Conclusion: The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs-PPARγ pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.

AB - Background: Epoxyeicosatrienoic acids (EETs) are natural angiogenic mediators regulated by soluble epoxide hydrolase (sEH). Inhibitors of sEH can stabilize EETs levels and were reported to reduce atherosclerosis and inhibit myocardial infarction in animal models. In this work, we investigated whether increasing EETs with the sEH inhibitor t-AUCB would increase angiogenesis related function in endothelial progenitor cells (EPCs) from patients with acute myocardial infarction (AMI). Methods and results: EPCs were isolated from 50 AMI patients and 50 healthy subjects (control). EPCs were treated with different concentrations of t-AUCB for 24 h with or without peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662. Migration of EPCs was assayed in trans-well chambers. Angiogenesis assays were performed using a Matrigel-Matrix in vitro model. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) mRNA and protein in EPCs was measured by real-time PCR or Western blot, respectively. Also, the concentration of EETs in the culture supernatant was detected by ELISA. The activity of EPCs in the AMI patient group was reduced compared to healthy controls. Whereas increasing EET levels with t-AUCB promoted a dose dependent angiogenesis and migration in EPCs from AMI patients. Additionally, the t-AUCB dose dependently increased the expression of the angiogenic factors VEGF and HIF-α. Lastly, we provide evidence that these effects were PPARγ dependent. Conclusion: The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs-PPARγ pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.

KW - Acute myocardial infarction

KW - Endothelial progenitor cells

KW - Soluble epoxide hydrolase inhibitor

KW - Vascular endothelial growth factor

UR - http://www.scopus.com/inward/record.url?scp=84880735525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880735525&partnerID=8YFLogxK

U2 - 10.1016/j.ijcard.2012.03.167

DO - 10.1016/j.ijcard.2012.03.167

M3 - Article

C2 - 22525341

AN - SCOPUS:84880735525

VL - 167

SP - 1298

EP - 1304

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

IS - 4

ER -