RGD Reference Report - Gene transfer of human prostacyclin synthase ameliorates monocrotaline-induced pulmonary hypertension in rats. - Rat Genome Database

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Gene transfer of human prostacyclin synthase ameliorates monocrotaline-induced pulmonary hypertension in rats.

Authors: Nagaya, N  Yokoyama, C  Kyotani, S  Shimonishi, M  Morishita, R  Uematsu, M  Nishikimi, T  Nakanishi, N  Ogihara, T  Yamagishi, M  Miyatake, K  Kaneda, Y  Tanabe, T 
Citation: Nagaya N, etal., Circulation. 2000 Oct 17;102(16):2005-10. doi: 10.1161/01.cir.102.16.2005.
RGD ID: 401959335
Pubmed: PMID:11034952   (View Abstract at PubMed)
DOI: DOI:10.1161/01.cir.102.16.2005   (Journal Full-text)


BACKGROUND: Prostacyclin is a potent vasodilator that also inhibits platelet adhesion and cell growth. We investigated whether in vivo gene transfer of human prostacyclin synthase (PGIS) ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats.
METHODS AND RESULTS: The cDNA encoding PGIS was intratracheally transfected into the lungs of rats by the hemagglutinating virus of Japan-liposome method. Rats transfected with control vector lacking the PGIS gene served as controls. Three weeks after MCT injection, mean pulmonary arterial pressure and total pulmonary resistance had increased significantly; the increases were significantly attenuated in PGIS gene-transfected rats compared with controls [mean pulmonary arterial pressure, 31+/-1 versus 35+/-1 mm Hg (-12%); total pulmonary resistance, 0.087+/-0.01 versus 0.113+/-0.01 mm Hg x mL x min(-1) x kg(-1) (-23%), both P:<0.05]. Systemic arterial pressure and heart rate were unaffected. Histologically, PGIS gene transfer inhibited the increase in medial wall thickness of peripheral pulmonary arteries that resulted from MCT injection. PGIS immunoreactivity was intense predominantly in the bronchial epithelium and alveolar cells. Lung tissue levels of 6-keto-PGF(1alpha), a stable metabolite of prostacyclin, were significantly increased for >/=1 week after transfer of PGIS gene. The Kaplan-Meier survival curves demonstrated that repeated transfer of PGIS gene every 2 weeks increased survival rate in MCT rats (log-rank test, P:<0.01).
CONCLUSIONS: Intratracheal transfer of the human PGIS gene augmented pulmonary prostacyclin synthesis, ameliorated MCT-induced pulmonary hypertension, and thereby improved survival in MCT rats.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanPulmonary Arterial Hypertension treatmentIMP human gene in a rat modelRGD 
PtgisRatPulmonary Arterial Hypertension treatmentISOPTGIS (Homo sapiens)human gene in a rat modelRGD 
PtgisMousePulmonary Arterial Hypertension treatmentISOPTGIS (Homo sapiens)human gene in a rat modelRGD 

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