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The CYP4A‐20‐HETE System in Regulation of Endothelial Progenitor Cell Functions
Author(s) -
guo austin meng,
Janic Branislave,
Arbab Ali S,
Edwards Paul A,
Scicli Alfonso Guillermo
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.965.18
Subject(s) - angiogenesis , matrigel , neovascularization , progenitor cell , endothelial progenitor cell , homing (biology) , endothelial stem cell , hydroxyeicosatetraenoic acid , umbilical vein , microbiology and biotechnology , chemistry , biology , cancer research , arachidonic acid , biochemistry , in vitro , stem cell , enzyme , ecology
Endothelial progenitor cells (EPC) are essential in the repair of impaired vascular perfusion because they contribute to neovascularization and wound healing. Cytochrome P450 4As are ω‐hydroxylases that metabolize arachidonic acid (AA) to 20‐hydroxyeicosatetraenoic acid (20‐HETE). We have reported that 20‐HETE is angiogenic and that inhibitors of 20‐HETE synthesis inhibit angiogenesis. In this study, we hypothesize that the CYP4A‐20‐HETE system regulates EPC functions. We found that the mRNA coding for CYP4A11, the main human 20‐HETE synthase is present in EPC isolated from human umbilical cords. These EPC contain large amounts of immunoreactive CYP4A11 and they form and secrete 20‐HETE when incubated with AA. Further, 20‐HETE increases EPC proliferation and migration, suggesting that EPC are a target for 20‐HETE. When matrigel plugs containing 20‐HETE are injected sc in nude mice, a marked angiogenic response is observed. Injection of EPC iv results in the accumulation of these EPC to the site of angiogenic response in the plug, suggesting that 20‐HETE may induce EPC homing. Additionally, 20‐HETE induces tube formation by human endothelial cell, and EPC appear to incorporate into the tube wall, suggesting that 20‐HETE facilitate EPC involvement in vessel formation. Thus the CYP4A‐20‐HETE system may be involved in regulation of EPC functions, a novel finding with potentially high clinical relevance.