RGD Reference Report - Antiangiogenic treatment with Sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats. - Rat Genome Database

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Antiangiogenic treatment with Sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats.

Authors: Tugues, S  Fernandez-Varo, G  Munoz-Luque, J  Ros, J  Arroyo, V  Rodes, J  Friedman, SL  Carmeliet, P  Jimenez, W  Morales-Ruiz, M 
Citation: Tugues S, etal., Hepatology. 2007 Dec;46(6):1919-26.
RGD ID: 1643338
Pubmed: PMID:17935226   (View Abstract at PubMed)
DOI: DOI:10.1002/hep.21921   (Journal Full-text)

Liver cirrhosis is a very complex disease in which several pathological processes such as inflammation, fibrosis, and pathological angiogenesis are closely integrated. We hypothesized that treatment with pharmacological agents with multiple mechanisms of action will produce superior results to those achieved by only targeting individual mechanisms. This study thus evaluates the therapeutic use of the multitargeted receptor tyrosine kinase inhibitor Sunitinib (SU11248). The in vitro effects of SU11248 were evaluated in the human hepatic stellate cell line LX-2 by measuring cell viability. The in vivo effects of SU11248 treatment were monitored in the livers of cirrhotic rats by measuring angiogenesis, inflammatory infiltrate, fibrosis, alpha-smooth muscle actin (alpha-SMA) accumulation, differential gene expression by microarrays, and portal pressure. Cirrhosis progression was associated with a significant enhancement of vascular density and expression of vascular endothelial growth factor-A, angiopoietin-1, angiopoietin-2, and placental growth factor in cirrhotic livers. The newly formed hepatic vasculature expressed vascular cellular adhesion molecule 1 and intercellular adhesion molecule 1. Interestingly, the expression of these adhesion molecules was adjacent to areas of local inflammatory infiltration. SU11248 treatment resulted in a significant decrease in hepatic vascular density, inflammatory infiltrate, alpha-SMA abundance, LX-2 viability, collagen expression, and portal pressure. Conclusion: These results suggest that multitargeted therapies against angiogenesis, inflammation, and fibrosis merit consideration in the treatment of cirrhosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Cirrhosis disease_progressionISOAngpt1 (Rattus norvegicus)1643338; 1643338protein:increased expression:liverRGD 
Experimental Liver Cirrhosis disease_progressionIEP 1643338protein:increased expression:liverRGD 
Experimental Liver Cirrhosis disease_progressionISOPgf (Rattus norvegicus)1643338; 1643338 RGD 
Experimental Liver Cirrhosis disease_progressionIEP 1643338 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Angpt1  (angiopoietin 1)
Pgf  (placental growth factor)

Genes (Mus musculus)
Angpt1  (angiopoietin 1)
Pgf  (placental growth factor)

Genes (Homo sapiens)
ANGPT1  (angiopoietin 1)
PGF  (placental growth factor)


Additional Information