- 作者：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
- 关键词：Soluble epoxide hydrolase inhibitor ; Acute myocardial infarction ; Endothelial progenitor cells ; Vascular endothelial growth factor
- 刊名：International Journal of Cardiology
- 出版年：2013
- 出版时间：20 August, 2013
- 年：2013
- 卷：167
- 期：4
- 页码：1298-1304
- 全文大小：1027 K
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 ¦Ã (PPAR¦Ã) 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 1¦Á (HIF-1¦Á) 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-¦Á. Lastly, we provide evidence that these effects were PPAR¦Ã dependent.
Conclusion
The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs-PPAR¦Ã pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.