The cytochrome P450 4A/F-20-hydroxyeicosatetraenoic acid system

A regulator of endothelial precursor cells derived from human umbilical cord blood

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Endothelial progenitor cells (EPCs) contribute to physiological and pathological neovascularization. Previous data have suggested that the cytochrome P450 4A/F (CYP4A/F)-20-hydroxyeicosatetraenoic acid (20-HETE) system regulates neovascularization. Therefore, we studied whether the angiogenic effects of the CYP4A/F-20-HETE system involve regulation of EPC function. We extracted human umbilical cord blood and isolated EPCs, which express AC133 +CD34+ and kinase insert domain receptor (KDR) surface markers and contain mRNA and protein for CYP4A11 and CYP4A22 enzymes, as opposed to mesenchymal stem cells, which only express negligible amounts of CYP4A11/22. When EPCs were incubated with arachidonic acid, they produced 20-HETE, which stimulated the cells to proliferate and migrate, as did vascular endothelial growth factor. Incubation with 1 μM N-hydroxy-N′-(4-butyl-2- methylphenyl)formamidine (HET0016), a selective inhibitor of 20-HETE synthesis, reduced the proliferative and migratory effects of vascular endothelial growth factor and also significantly abolished EPC migration mediated by stroma-derived factor-1α, as did (6,15) 20-hydroxyeicosadienoic acid. Coculturing EPCs and endothelial cells on a Matrigel matrix led to tube formation, which in turn was inhibited by both HET0016 and 20-hydroxyeicosadienoic acid. We concluded that the CYP4A/F-20-HETE system is expressed in EPCs and can act as both an autocrine and a paracrine regulatory factor.

Original languageEnglish (US)
Pages (from-to)421-429
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume338
Issue number2
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Fingerprint

Fetal Blood
Cytochrome P-450 Enzyme System
Endothelial Cells
Vascular Endothelial Growth Factor A
Physiologic Neovascularization
Pathologic Neovascularization
Vascular Endothelial Growth Factor Receptor-2
Acids
Endothelial Progenitor Cells
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Mesenchymal Stromal Cells
Arachidonic Acid
Cell Movement
Messenger RNA
Enzymes
Proteins

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

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 A.; Arbab, Ali Syed; Scicli, A. Guillermo.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 338, No. 2, 01.08.2011, p. 421-429.

Research output: Contribution to journalArticle

Guo, Austin M. ; Janic, Branislava ; Sheng, Ju ; Falck, John R. ; Roman, Richard J. ; Edwards, Paul A. ; Arbab, Ali Syed ; Scicli, A. Guillermo. / The cytochrome P450 4A/F-20-hydroxyeicosatetraenoic acid system : A regulator of endothelial precursor cells derived from human umbilical cord blood. In: Journal of Pharmacology and Experimental Therapeutics. 2011 ; Vol. 338, No. 2. pp. 421-429.
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