RGD Reference Report - Prostacyclin synthase gene transfer inhibits neointimal formation by suppressing PPAR delta expression. - Rat Genome Database

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Prostacyclin synthase gene transfer inhibits neointimal formation by suppressing PPAR delta expression.

Authors: Imai, Hajime  Numaguchi, Yasushi  Ishii, Masakazu  Kubota, Ryuji  Yokouchi, Kazuhiko  Ogawa, Yasuhiro  Kondo, Takahisa  Okumura, Kenji  Murohara, Toyoaki 
Citation: Imai H, etal., Atherosclerosis. 2007 Dec;195(2):322-32. doi: 10.1016/j.atherosclerosis.2007.01.010. Epub 2007 Feb 14.
RGD ID: 401959382
Pubmed: PMID:17303142   (View Abstract at PubMed)
DOI: DOI:10.1016/j.atherosclerosis.2007.01.010   (Journal Full-text)


OBJECTIVE: Prostacyclin (PGI(2)) is a potent ligand of peroxisome proliferator-activated receptor delta (PPAR delta) that regulates cell growth and differentiation. The aim of this study was to elucidate how endogenous PGI(2) overexpression affects the expressions of PPAR delta and mitogen-activated protein kinases (MAPKs) in the development of neointimal formation in experimental angioplasty with adenovirus-mediated PGI(2) synthase (Ad-PGIS) gene transfer.
METHODS AND RESULTS: In human aortic smooth muscle cells, protein blotting analysis showed that PGI(2) overproduction decreased the levels of phosphorylated p38 MAPK (P-p38 MAPK) (2.0-fold versus 0.83-fold relative to control). Immunohistochemical analysis in balloon-injured arteries revealed diffuse expression of PPAR delta in the neointima of control vessels, with no expression in uninjured vessels. The level of PPAR delta expression was lower in Ad-PGIS-treated arteries than in control vessels, with the PPAR delta localized in the neointima adjacent to endothelium. Staining of P-p38 MAPK showed a similar pattern to PPAR delta among the three groups. Morphometric analysis at day 14 revealed that Ad-PGIS reduced the intima-to-media ratio by up to 59%.
CONCLUSIONS: Ad-PGIS gene transfer reduced PPAR delta expression and inhibited neointimal formation after balloon injury in accordance with the reduction in the phosphorylation of p38 MAPK.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanCarotid Artery Injuries treatmentISOPtgis (Rattus norvegicus) RGD 
PtgisRatCarotid Artery Injuries treatmentIMP  RGD 
PtgisMouseCarotid Artery Injuries treatmentISOPtgis (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PtgisRatnegative regulation of protein phosphorylation  IMP p38 MAPKRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)


Additional Information