PMID- 34548575
OWN - NLM
STAT- MEDLINE
DCOM- 20211230
LR  - 20230206
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Sep 21
TI  - Cyp2c44 epoxygenase-derived epoxyeicosatrienoic acids in vascular smooth muscle 
      cells elicit vasoconstriction of the murine ophthalmic artery.
PG  - 18764
LID - 10.1038/s41598-021-98236-w [doi]
LID - 18764
AB  - 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.
CI  - (c) 2021. The Author(s).
FAU - Hu, Jiong
AU  - Hu J
AD  - Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe 
      University, Frankfurt, Germany.
AD  - German Centre of Cardiovascular Research (DZHK), Partner site RheinMain, 
      Frankfurt, Germany.
FAU - Sisignano, Marco
AU  - Sisignano M
AD  - Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, University 
      Hospital, Goethe-University, Frankfurt, Germany.
AD  - Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, 
      Germany.
FAU - Brecht, Roman
AU  - Brecht R
AD  - Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg 
      University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
FAU - Perumal, Natarajan
AU  - Perumal N
AUID- ORCID: 0000-0002-2612-5907
AD  - Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg 
      University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
FAU - Angioni, Carlo
AU  - Angioni C
AD  - Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, University 
      Hospital, Goethe-University, Frankfurt, Germany.
FAU - Bibli, Iris-Sofia
AU  - Bibli IS
AD  - Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe 
      University, Frankfurt, Germany.
AD  - German Centre of Cardiovascular Research (DZHK), Partner site RheinMain, 
      Frankfurt, Germany.
FAU - Fisslthaler, Beate
AU  - Fisslthaler B
AD  - Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe 
      University, Frankfurt, Germany.
AD  - German Centre of Cardiovascular Research (DZHK), Partner site RheinMain, 
      Frankfurt, Germany.
FAU - Kleinert, Hartmut
AU  - Kleinert H
AD  - Department of Pharmacology, University Medical Centre of the Johannes Gutenberg 
      University Mainz, Mainz, Germany.
FAU - Pfeiffer, Norbert
AU  - Pfeiffer N
AD  - Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg 
      University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
FAU - Fleming, Ingrid
AU  - Fleming I
AD  - Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe 
      University, Frankfurt, Germany.
AD  - German Centre of Cardiovascular Research (DZHK), Partner site RheinMain, 
      Frankfurt, Germany.
FAU - Manicam, Caroline
AU  - Manicam C
AUID- ORCID: 0000-0001-5891-1155
AD  - Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg 
      University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. 
      caroline.manicam@unimedizin-mainz.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210921
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - EC 1.14.14.1 (Cyp2c23 protein, mouse)
RN  - EC 1.14.14.1 (Cytochrome P450 Family 2)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - EC 3.3.2.10 (Ephx2 protein, mouse)
RN  - UDX6WPL94T (eicosenoic acid)
SB  - IM
MH  - Animals
MH  - Cytochrome P450 Family 2/*chemistry/metabolism
MH  - Epoxide Hydrolases/metabolism
MH  - Fatty Acids, Monounsaturated/chemistry/*pharmacology
MH  - Mice
MH  - Ophthalmic Artery/*drug effects/enzymology/physiology
MH  - Vasoconstriction/*drug effects
PMC - PMC8455677
COIS- The authors declare no competing interests.
EDAT- 2021/09/23 06:00
MHDA- 2021/12/31 06:00
PMCR- 2021/09/21
CRDT- 2021/09/22 06:47
PHST- 2021/06/11 00:00 [received]
PHST- 2021/09/02 00:00 [accepted]
PHST- 2021/09/22 06:47 [entrez]
PHST- 2021/09/23 06:00 [pubmed]
PHST- 2021/12/31 06:00 [medline]
PHST- 2021/09/21 00:00 [pmc-release]
AID - 10.1038/s41598-021-98236-w [pii]
AID - 98236 [pii]
AID - 10.1038/s41598-021-98236-w [doi]
PST - epublish
SO  - Sci Rep. 2021 Sep 21;11(1):18764. doi: 10.1038/s41598-021-98236-w.