Role of M üller cell cytochrome P450 2c44 in murine retinal angiogenesis

Publication date: November 2017 Source:Prostaglandins & Other Lipid Mediators, Volume 133 Author(s): Jiong Hu, Alexandra Geyer, Sarah Dziumbla, Khader Awwad, Darryl C. Zeldin, Wolf-Hagen Schunck, Rüdiger Popp, Timo Frömel, Ingrid Fleming Polyunsaturated fatty acids (PUFA) and their cytochrome P450 (CYP450) metabolites have been linked to angiogenesis and vessel homeostasis. However, the role of individual CYP isoforms and their endogenous metabolites in those processes are not clear. Here, we focused on the role of Cyp2c44 in postnatal retinal angiogenesis and report that Cyp2c44 is highly expressed in Müller glial cells in the retina. The constitutive as well as inducible postnatal genetic deletion of Cyp2c44 resulted in an increased vessel network density without affecting vessel radial expansion during the first postnatal week. This phenotype was associated with an increased endothelial cell proliferation and attenuated Notch signaling. LC–MS/MS analyses revealed that levels of hydroxydocosahexaenoic acids (HDHA), i.e., 10-, 17- and 20-HDHA were significantly elevated in retinas from 5day old Cyp2c44−/− mice compared to their wild-type littermates. Enzymatic activity assays revealed that HDHAs were potential substrates for Cyp2c44 which could account for the increased levels of HDHAs in retinas from Cyp2c44−/− mice. These data indicate that Cyp2c44 is expressed in the murine retina and, like the soluble epoxide hydrolase, is expressed in Mü...
Source: Prostaglandins and Other Lipid Mediators - Category: Lipidology Source Type: research