RGD Reference Report - Repeated gene transfer of naked prostacyclin synthase plasmid into skeletal muscles attenuates monocrotaline-induced pulmonary hypertension and prolongs survival in rats. - Rat Genome Database

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Repeated gene transfer of naked prostacyclin synthase plasmid into skeletal muscles attenuates monocrotaline-induced pulmonary hypertension and prolongs survival in rats.

Authors: Tahara, N  Kai, H  Niiyama, H  Mori, T  Sugi, Y  Takayama, N  Yasukawa, H  Numaguchi, Y  Matsui, H  Okumura, K  Imaizumi, T 
Citation: Tahara N, etal., Hum Gene Ther. 2004 Dec;15(12):1270-8.
RGD ID: 1580695
Pubmed: PMID:15684702   (View Abstract at PubMed)
DOI: DOI:10.1089/hum.2004.15.1270   (Journal Full-text)

A safer, less invasive method for repeated transgene administration is desirable for clinical application of gene therapy targeting chronic diseases, including pulmonary hypertension (PH). Thus, effects of prostaglandin I2 (prostacyclin) synthase (PGIS) gene transfer by the naked DNA method into skeletal muscle were investigated in monocrotaline (MCT)-induced PH rats. A single injection of rat PGIS cDNA-encoding plasmid into thigh muscle 3 days after bupivacaine pretreatment transiently increased muscle PGIS protein expression and muscle and serum levels of a stable prostacyclin metabolite (6-keto-prostaglandin F1). The muscle 6-keto-prostaglandin F1 level peaked on day 2 but was still elevated on day 7; prostacyclin selectively increased lung cyclic AMP levels as compared with liver and kidney. MCT induced a marked rise in right ventricular (RV) systolic pressure, pulmonary arterial wall thickening, and RV hypertrophy. Repeated PGIS gene transfer every week lowered RV systolic pressure and ameliorated RV and pulmonary artery remodeling in MCT-induced PH rats. Furthermore, repeated PGIS gene transfer significantly improved the survival rate of MCT-induced PH rats. In conclusion, repeated PGIS gene transfer into skeletal muscle not only attenuated the development of PH and cardiovascular remodeling but also improved the prognosis for MCT-induced PH rats. This study may provide insight into a new treatment strategy for PH.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanpulmonary hypertension treatmentISOPtgis (Rattus norvegicus) RGD 
PtgisRatpulmonary hypertension treatmentIMP  RGD 
PtgisMousepulmonary hypertension treatmentISOPtgis (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PtgisRatprostaglandin biosynthetic process  IMP  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