The Cytochrome P450 4A/F-20-Hydroxyeicosatetraenoic Acid System: A Regulator of Endothelial Precursor Cells Derived from Human Umbilical Cord Blood

Guo, Austin M.; Janic, Branislava; Sheng, Ju; Falck, John R.; Roman, Richard J.; Edwards, Paul; Arbab, Ali S.; Scicli, A. G.

doi:10.1124/jpet.111.179036

Cited by 38 publications

(56 citation statements)

References 40 publications

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“…On the other hand, Amaral et al (2003) found that 20-HETE lies downstream of the VEGF signaling pathway for angiogenesis in skeletal muscles . In addition, the selective 20-HETE synthesis inhibitor HET0016 blocks VEGF-induced EPC proliferation and migration (Guo et al, 2011) and VEGFmediated corneal neovascularization (Chen et al, 2005). These data are consistent with 20-HETE being downstream of the VEGF pathway.…”

Section: Introductionsupporting

confidence: 76%

“…20-HETE induces the expression of HIF-1a and its downstream target VEGF in EPC and EC (Guo et al, 2007(Guo et al, , 2009(Guo et al, , 2011. Production of SDF1a and VEGF is regulated by upstream HIF-1a (Ceradini et al, 2004;De Falco et al, 2004;Hoenig et al, 2008), and 20-HETE increases the expression of both SDF-1 and VEGF (Guo et al, 2011), suggesting that 20-HETE may be upstream of VEGF. On the other hand, Amaral et al (2003) found that 20-HETE lies downstream of the VEGF signaling pathway for angiogenesis in skeletal muscles .…”

Section: Introductionmentioning

confidence: 98%

“…It is primarily found in the microcirculation of the kidney, liver, and brain (Carroll et al, 1997;Miyata and Roman, 2005). Studies in our laboratory identified the CYP4A11-20-HETE system as a novel regulator of several EPC functions associated with the neovascularization response (Guo et al, 2011). It promotes EPC proliferation, migration, and secretion of proangiogenic molecules, such as hypoxia-inducible factor-1-a(HIF-1a), vascular endothelial growth factor (VEGF), and stroma-derived factor (SDF)-1, as well as EPC-mediated endothelial cell tube formation (Guo et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Studies in our laboratory identified the CYP4A11-20-HETE system as a novel regulator of several EPC functions associated with the neovascularization response (Guo et al, 2011). It promotes EPC proliferation, migration, and secretion of proangiogenic molecules, such as hypoxia-inducible factor-1-a(HIF-1a), vascular endothelial growth factor (VEGF), and stroma-derived factor (SDF)-1, as well as EPC-mediated endothelial cell tube formation (Guo et al, 2011). Furthermore, 20-HETE increases EC proliferation and migration; both are essential steps in the angiogenic cascade (Guo et al, 2007;Jiang et al, 2004;Guo et al, 2009), However, the underlying cellular mechanisms by which 20-HETE regulates EPC angiogenic functions and its contribution to physiologic and pathologic neovascularization in vivo is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

“…The major chemokines and corresponding cell surface receptors that regulate EPC mobilization, adhesion, and chemotaxis are SDF-1 and chemokine receptor type 4 (CXCR4) (Hidalgo et al, 2001;De Falco et al, 2004;Guo et al, 2011). VEGF plays a critical role in the regulation of EPC function by increasing mobilization of EPC from the bone marrow and mediating their migration into the circulation (Li et al, 2006;Rosti et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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20-HETE Regulates the Angiogenic Functions of Human Endothelial Progenitor Cells and Contributes to Angiogenesis In Vivo

Chen

Ackerman

Saleh

et al. 2014

J Pharmacol Exp Ther

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Circulating endothelial progenitor cells (EPC) contribute to postnatal neovascularization. We identified the cytochrome P450 4A/ F-20-hydroxyeicosatetraenoic acid (CYP4A/F-20-HETE) system as a novel regulator of EPC functions associated with angiogenesis in vitro. Here, we explored cellular mechanisms by which 20-HETE regulates EPC angiogenic functions and assessed its contribution to EPC-mediated angiogenesis in vivo. Results showed that both hypoxia and vascular endothelial growth factor (VEGF) induce CYP4A11 gene and protein expression (the predominant 20-HETE synthases in human EPC), and this is accompanied by an increase in 20-HETE production by ∼1.4-and 1.8-fold, respectively, compared with the control levels. Additional studies demonstrated that 20-HETE and VEGF have a synergistic effect on EPC proliferation, whereas 20-HETE antagonist 20-HEDGE or VEGF-neutralizing antibody negated 20-HETE-or VEGF-induced proliferation, respectively. These findings are consistent with the presence of a positive feedback regulation on EPC proliferation between the 20-HETE and the VEGF pathways. Furthermore, we found that 20-HETE induced EPC adhesion to fibronectin and endothelial cell monolayer by 40 6 5.6 and 67 6 10%, respectively, which was accompanied by a rapid induction of very late antigen-4 and chemokine receptor type 4 mRNA and protein expression. Basal and 20-HETEstimulated increases in adhesion were negated by the inhibition of the CYP4A-20-HETE system. Lastly, EPC increased angiogenesis in vivo by 3.6 6 0.2-fold using the Matrigel plug angiogenesis assay, and these increases were markedly reduced by the local inhibition of 20-HETE system. These results strengthened the notion that 20-HETE regulates the angiogenic functions of EPC in vitro and EPC-mediated angiogenesis in vivo.

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Section: Introductionsupporting

confidence: 76%