RGD Reference Report - Cytochrome P450 subfamily 2J polypeptide 2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Cytochrome P450 subfamily 2J polypeptide 2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia.

Authors: Herse, F  Lamarca, B  Hubel, CA  Kaartokallio, T  Lokki, AI  Ekholm, E  Laivuori, H  Gauster, M  Huppertz, B  Sugulle, M  Ryan, MJ  Novotny, S  Brewer, J  Park, JK  Kacik, M  Hoyer, J  Verlohren, S  Wallukat, G  Rothe, M  Luft, FC  Muller, DN  Schunck, WH  Staff, AC  Dechend, R 
Citation: Herse F, etal., Circulation. 2012 Dec 18;126(25):2990-9. doi: 10.1161/CIRCULATIONAHA.112.127340. Epub 2012 Nov 15.
RGD ID: 7243127
Pubmed: PMID:23155181   (View Abstract at PubMed)
PMCID: PMC3543781   (View Article at PubMed Central)
DOI: DOI:10.1161/CIRCULATIONAHA.112.127340   (Journal Full-text)

BACKGROUND: Preeclampsia is a multisystem disorder of pregnancy, originating in the placenta. Cytochrome P450 (CYP)-dependent eicosanoids regulate vascular function, inflammation, and angiogenesis, which are mechanistically important in preeclampsia. METHODS AND RESULTS: We performed microarray screening of placenta and decidua (maternal placenta) from 25 preeclamptic women and 23 control subjects. The CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in preeclamptic placenta and decidua. Reverse-transcription polymerase chain reaction confirmed the upregulation, and immunohistochemistry localized CYP2J2 in trophoblastic villi and deciduas at 12 weeks and term. The CYP2J2 metabolites, 5,6-epoxyeicosatrienoic acid (EET), 14,15-EET, and the corresponding dihydroxyeicosatrienoic acids, were elevated in preeclamptic women compared with controls in the latter two thirds of pregnancy and after delivery. Stimulating a trophoblast-derived cell line with the preeclampsia-associated cytokine tumor necrosis factor-alpha enhanced CYP2J2 gene and protein expression. In 2 independent rat models of preeclampsia, reduced uterine-perfusion rat and the transgenic angiotensin II rat, we observed elevated EET, dihydroxyeicosatrienoic acid, and preeclamptic features that were ameliorated by the CYP epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MsPPOH). Uterine arterial rings of these rats also dilated in response to MsPPOH. Furthermore, 5,6-EET could be metabolized to a thromboxane analog. In a bioassay, 5,6-EET increased the beating rate of neonatal cardiomyocytes. Blocking thromboxane synthesis reversed that finding and also normalized large-conductance calcium-activated potassium channel activity. CONCLUSIONS: Our data implicate CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the disturbed uteroplacental remodeling, leading to hypertension and endothelial dysfunction.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pre-eclampsia  ISOCyp2j4 (Rattus norvegicus)7243127; 7243127 RGD 
pre-eclampsia  IEP 7243127mRNA:increased expression:placenta and deciduaRGD 
pre-eclampsia  ISOCYP2J2 (Homo sapiens)7243127; 7243127mRNA:increased expression:placenta and deciduaRGD 
pre-eclampsia  IMP 7243127 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp2j4  (cytochrome P450, family 2, subfamily j, polypeptide 4)

Genes (Mus musculus)
Cyp2j6  (cytochrome P450, family 2, subfamily j, polypeptide 6)

Genes (Homo sapiens)
CYP2J2  (cytochrome P450 family 2 subfamily J member 2)


Additional Information