RGD Reference Report - Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension. - Rat Genome Database

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Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension.

Authors: Yu, Q  Shao, R  Qian, H S  George, S E  Rockey, D C 
Citation: Yu Q, etal., J Clin Invest. 2000 Mar;105(6):741-8. doi: 10.1172/JCI7997.
RGD ID: 13824993
Pubmed: PMID:10727442   (View Abstract at PubMed)
PMCID: PMC377460   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI7997   (Journal Full-text)

Reduced production of nitric oxide (NO) in the cirrhotic liver results from a defect in hepatic endothelial cell nitric oxide synthase (ecNOS) and appears to contribute to the high intrahepatic resistance and portal hypertension typical of cirrhosis. Therefore, we postulated that targeting a heterologous NOS isoform to sinusoidal endothelial cells or other perisinusoidal cells, such as hepatic stellate cells, would counter the defect in NO production and reduce resistance to blood flow. Recombinant adenovirus (Ad) carrying the neuronal NOS gene (nNOS) targeted liver sinusoidal endothelial cells, stellate cells, and hepatocytes more efficiently than the corresponding cells in cirrhotic livers, but transduction rates were substantial even in cirrhotic animals. Expression of nNOS in each liver cell type, whether from normal or injured liver, caused increased NO production and inhibited endothelin-1-induced contractility of perisinusoidal stellate cells. Finally, in 2 different in vivo models of cirrhosis and portal hypertension, transduction of livers with recombinant Ad.nNOS significantly reduced intrahepatic resistance and portal pressure. The data highlight the feasibility of gene transfer to diseased liver and hepatic cells and demonstrate the potential of a novel therapy for portal hypertension caused by cirrhosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
portal hypertension treatmentISONos1 (Rattus norvegicus)13824993; 13824993associated with liver cirrhosisRGD 
portal hypertension treatmentIDA 13824993associated with liver cirrhosisRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of hepatic stellate cell contraction  IDA 13824993 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos1  (nitric oxide synthase 1)

Genes (Mus musculus)
Nos1  (nitric oxide synthase 1, neuronal)

Genes (Homo sapiens)
NOS1  (nitric oxide synthase 1)

Additional Information