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
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Article info
Publication history
Published online: April 23, 2012
Accepted:
March 30,
2012
Received in revised form:
March 21,
2012
Received:
August 7,
2011
Identification
Copyright
© 2012 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
