TY  - JOUR
A1  - Hu, Jiong
A1  - Sisignano, Marco
A1  - Brecht, Roman
A1  - Perumal, Natarajan
A1  - Angioni, Carlo
A1  - Bibli, Sofia Iris
A1  - Fißlthaler, Beate
A1  - Kleinert, Hartmut
A1  - Pfeiffer, Norbert
A1  - Fleming, Ingrid
A1  - Manicam, Caroline
T1  - Cyp2c44 epoxygenase-derived epoxyeicosatrienoic acids in vascular smooth muscle cells elicit vasoconstriction of the murine ophthalmic artery
T2  - Scientific reports
N2  - Cytochrome P450 (CYP) signalling pathway has been shown to play a vital role in the vasoreactivity of wild type mouse ophthalmic artery. In this study, we determined the expression, vascular responses and potential mechanisms of the CYP-derived arachidonic acid metabolites. The expression of murine CYP (Cyp2c44) and soluble epoxide hydrolase (sEH) in the wild type ophthalmic artery was determined with immunofluorescence, which showed predominant expression of Cyp2c44 in the vascular smooth muscle cells (VSMC), while sEH was found mainly in the endothelium of the wild type ophthalmic artery. Artery of Cyp2c44−/− and sEH−/− mice were used as negative controls. Targeted mass spectrometry-based lipidomics analysis of endogenous epoxide and diols of the wild type artery detected only 14, 15-EET. Vasorelaxant responses of isolated vessels in response to selective pharmacological blockers and agonist were analysed ex vivo. Direct antagonism of epoxyeicosatrienoic acids (EETs) with a selective inhibitor caused partial vasodilation, suggesting that EETs may behave as vasoconstrictors. Exogenous administration of synthetic EET regioisomers significantly constricted the vessels in a concentration-dependent manner, with the strongest responses elicited by 11, 12- and 14, 15-EETs. Our results provide the first experimental evidence that Cyp2c44-derived EETs in the VSMC mediate vasoconstriction of the ophthalmic artery.
KW  - Animal disease models
KW  - Glaucoma
KW  - Immunohistochemistry
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/64557
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-645577
SN  - 2045-2322
N1  - This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) grant (MA 8006/1-1) to Caroline Manicam. Marco Sisignano is supported by Grants SFB1039 A09 and Z01 of the DFG as well as the Fraunhofer Foundation Project: Neuropathic Pain. Natarajan Perumal is supported by DFG grant (PE 2531/4-1). Ingrid Fleming is supported by DFG grant (SFB 834/B13). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
N1  - Open Access funding enabled and organized by Projekt DEAL.
VL  - 11
IS  - art. 18764
SP  - 1
EP  - 14
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -