RGD Reference Report - Association between prostaglandin E receptor subtype EP4 overexpression and unstable phenotype in atherosclerotic plaques in human. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Association between prostaglandin E receptor subtype EP4 overexpression and unstable phenotype in atherosclerotic plaques in human.

Authors: Cipollone, F  Fazia, ML  Iezzi, A  Cuccurullo, C  De Cesare, D  Ucchino, S  Spigonardo, F  Marchetti, A  Buttitta, F  Paloscia, L  Mascellanti, M  Cuccurullo, F  Mezzetti, A 
Citation: Cipollone F, etal., Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1925-31. Epub 2005 Jul 14.
RGD ID: 1581284
Pubmed: PMID:16020747   (View Abstract at PubMed)
DOI: DOI:10.1161/01.ATV.0000177814.41505.41   (Journal Full-text)

OBJECTIVE: We recently demonstrated that inducible cyclooxygenase/PGE synthase-1 (COX-2/mPGES-1) are overexpressed in symptomatic plaques in association with PGE2-dependent metalloproteinase (matrix metalloproteinase [MMP]) biosynthesis and plaque rupture. However, it is not known which of the 4 PGE2 receptors (EP1-4) mediates macrophage metalloproteinase generation. The aim of this study was to characterize EP1-4 expression in plaques from symptomatic and asymptomatic patients undergoing carotid endarterectomy and correlate it with the extent of inflammatory infiltration, COX-2/mPGES-1 and MMP expression and clinical features of patients' presentation. METHODS AND RESULTS: Plaques were analyzed for COX-2, mPGES-1, EP1-4, MMP-2, and MMP-9 by immunohistochemistry, reverse-transcription polymerase chain reaction and Western blot; zymography was used to detect MMP activity. We observed strong EP4 immunoreactivity, only very weak staining for EP2, and no expression of EP1 and EP3 in atherosclerotic plaques. EP4 was more abundant in MMP-rich symptomatic lesions, whereas EP2 was no different between symptomatic and asymptomatic plaques. Finally, MMP induction by PGE2 in vitro was inhibited by the EP4 antagonist L-161 982, but not by its inactive analog L-161 983 or by the EP2 antagonist AH6809. CONCLUSIONS: This study shows that EP4 overexpression is associated with enhanced inflammatory reaction in atherosclerotic plaques. This effect might contribute to plaque destabilization by inducing culprit metalloproteinase expression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
arteriosclerosis  IAGP 1581284 RGD 
arteriosclerosis  ISOPTGER4 (Homo sapiens)1581284; 1581284 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptger4  (prostaglandin E receptor 4)

Genes (Mus musculus)
Ptger4  (prostaglandin E receptor 4 (subtype EP4))

Genes (Homo sapiens)
PTGER4  (prostaglandin E receptor 4)


Additional Information