RGD Reference Report - Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats. - Rat Genome Database

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Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats.

Authors: Ito, Takayuki  Okada, Takashi  Mimuro, Jun  Miyashita, Hiroshi  Uchibori, Ryosuke  Urabe, Masashi  Mizukami, Hiroaki  Kume, Akihiro  Takahashi, Masafumi  Ikeda, Uichi  Sakata, Yoichi  Shimada, Kazuyuki  Ozawa, Keiya 
Citation: Ito T, etal., Hypertension. 2007 Sep;50(3):531-6. doi: 10.1161/HYPERTENSIONAHA.107.091348. Epub 2007 Jul 16.
RGD ID: 401901195
Pubmed: PMID:17635855   (View Abstract at PubMed)
DOI: DOI:10.1161/HYPERTENSIONAHA.107.091348   (Journal Full-text)

Prostacyclin synthase (PGIS) is the final committed enzyme in the metabolic pathway of prostacyclin production. The therapeutic option of intravenous prostacyclin infusion in patients with pulmonary arterial hypertension is limited by the short half-life of the drug and life-threatening catheter-related complications. To develop a better delivery system for prostacyclin, we examined the feasibility of intramuscular injection of an adenoassociated virus (AAV) vector expressing PGIS for preventing monocrotaline-induced pulmonary arterial hypertension in rats. We developed an AAV serotype 1-based vector carrying a human PGIS gene (AAV-PGIS). AAV-PGIS or the control AAV vector expressing enhanced green fluorescent protein was injected into the anterior tibial muscles of 3-week-old male Wistar rats; this was followed by the monocrotaline administration at 7 weeks. Eight weeks after injecting the vector, the plasma levels of 6-keto-prostaglandin F(1alpha) increased in a vector dose-dependent manner. At this time point, the PGIS transduction (1x10(10) genome copies per body) significantly decreased mean pulmonary arterial pressure (33.9+/-2.4 versus 46.1+/-3.0 mm Hg; P<0.05), pulmonary vascular resistance (0.26+/-0.03 versus 0.41+/-0.03 mm Hg x mL(-1) x min(-1) x kg(-1); P<0.05), and medial thickness of the peripheral pulmonary artery (14.6+/-1.5% versus 23.5+/-0.5%; P<0.01) as compared with the controls. Furthermore, the PGIS-transduced rats demonstrated significantly improved survival rates as compared with the controls (100% versus 50%; P<0.05) at 8 weeks postmonocrotaline administration. An intramuscular injection of AAV-PGIS prevents monocrotaline-pulmonary arterial hypertension in rats and provides a new therapeutic alternative for preventing pulmonary arterial hypertension in humans.



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