RGD Reference Report - Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal formation in rat carotid arteries after balloon injury. - Rat Genome Database

Send us a Message



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

Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal formation in rat carotid arteries after balloon injury.

Authors: Numaguchi, Y  Naruse, K  Harada, M  Osanai, H  Mokuno, S  Murase, K  Matsui, H  Toki, Y  Ito, T  Okumura, K  Hayakawa, T 
Citation: Numaguchi Y, etal., Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):727-33. doi: 10.1161/01.atv.19.3.727.
RGD ID: 401960092
Pubmed: PMID:10073980   (View Abstract at PubMed)
DOI: DOI:10.1161/01.atv.19.3.727   (Journal Full-text)

Prostacyclin (PGI2), a metabolite of arachidonic acid, has the vasoprotective effects of vasodilation, anti-platelet aggregation, and inhibition of smooth muscle cell proliferation. We hypothesized that an overexpression of endogenous PGI2 may accelerate the recovery from endothelial damage and inhibit neointimal formation in the injured artery. To test this hypothesis, we investigated in vivo transfer of the PGI2 synthase (PCS) gene into balloon-injured rat carotid arteries by a nonviral lipotransfection method. Seven days after transfection, a significant regeneration of endothelium was observed in the arteries transfected with a plasmid carrying the rat PCS gene (pCMV-PCS), but little regeneration was seen in those with the control plasmid carrying the lacZ gene (pCMV-lacZ) (percent luminal circumference lined by newly regenerated endothelium: 87. 1+/-6.9% in pCMV-PCS-transfected vessels and 6.9+/-0.2% in pCMV-lacZ vessels, P<0.001). BrdU staining of arterial segments demonstrated a significantly lower incorporation in pCMV-PCS-transfected vessels (7. 5+/-0.3% positive nuclei in vessel cells) than in pCMV-lacZ (50. 7+/-9.6%, P<0.01). Moreover, 2 weeks after transfection, the PCS gene transfer resulted in a significant inhibition of neointimal formation (88% reduction in ratio of intima/media areas), whereas medial area was similar among the groups. Arterial segments transfected with pCMV-PCS produced significantly higher levels of 6-keto-PGF1alpha, the main metabolite of PGI2, compared with the segments transfected with pCMV-lacZ (10.2+/-0.55 and 2.1+/-0.32 ng/mg tissue for pCMV-PCS and pCMV-placZ, P<0.001). In conclusion, this study demonstrated that an in vivo PCS gene transfer increased the production of PGI2 and markedly inhibited neointimal formation with accelerated reendothelialization in rat carotid arteries after balloon injury.



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 smooth muscle cell proliferation  IMP  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanprostacyclin biosynthetic pathway  ISOPtgis (Rattus norvegicus) RGD 
PtgisRatprostacyclin biosynthetic pathway  IMP  RGD 
PtgisMouseprostacyclin biosynthetic pathway  ISOPtgis (Rattus norvegicus) RGD 
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