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Endothelium CYP1B1 Expression Mediates a Proangiogenic Phenotype
Author(s) -
Sheibani Nader,
Tang Yixin,
Sorenson. Christine M
Publication year - 2008
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.22.1_supplement.49.1
Subject(s) - cyp1b1 , retinal , biology , microbiology and biotechnology , angiogenesis , cytochrome p450 , biochemistry , enzyme , cancer research
Cytochrome P450 (CYP) enzymes catalyze mono‐oxygenase reactions, which not only facilitate excretion of foreign and endogenous lipophilic compounds, but also affect synthesis of physiologically active chemicals. Metabolisms of arachidonic acid by CYP4A and 2C subfamilies generate intermediates with distinct roles in modulation of vascular tone and angiogenesis. CYP1B1 is expressed in endothelial cells (EC) including those in the retina. Furthermore, CYP1B1 deficiency has been associated with abnormal ocular development in the human and mouse. To gain insight into the role CYP1B1 plays in EC function, we have isolated retinal EC from CYP1B1+/+ and CYP1B1−/− mice. We show that CYP1B1−/− retinal EC are less adherent, less migratory, and fail to undergo capillary morphogenesis in Matrigel. CYP1B1−/− retinal EC expressed high levels of thrombospondin‐2 (TSP2) in their culture medium, which was almost absent in medium from CYP1B1+/+ retinal EC. TSP2 is a matricellular protein with potent antiangiogenic activity. Re‐expression of CYP1B1 in CYP1B1−/− retinal EC improved their ability to undergo capillary morphogenesis, and resulted in down‐regulation of TSP2 expression. Our data together indicate that CYP1B1 metabolism of endogenous substrates greatly impacts the EC adhesive and migratory phenotype, at least in part, through suppression of TSP2 production in retinal EC.