Transcriptomics,Genomics

Dataset Information

29

SIMVASTATIN ATTENUATES LIVER INJURY IN RODENTS WITH BILIARY CIRRHOSIS SUBMITTED TO HEMORRHAGE/RESUSCITATION


ABSTRACT: In variceal bleeding liver function deterioration is a major cause of death. The effects of bleeding on intrahepatic microvascular dysfunction, which contributes to liver injury in cirrhosis, are largely unknown. The aims of this study were to evaluate the impact of hemorrhage/resuscitation (H/R) on cirrhotic microcirculation, and whether simvastatin, a drug that improves liver microcirculation, has hepatoprotective effects. The study was performed in three groups of rats: controls, rats with biliary cirrhosis (CBDL) and CBDL rats pre-treated with 3 doses (5 mg*Kg-1*day-1) of simvastatin. Rats were submitted to H/R or sham procedure. Subsequently, livers were isolated and perfused for functional assessment of liver microcirculation. Liver transcriptome was assessed with microarrays. H/R significantly impaired endothelial-dependent vasorelaxation in cirrhotic (p=0.035) but not control livers. H/R induced a similar increase in ALT in control and cirrhotic rats, whereas the increase in AST was 10 times higher in cirrhotic than in control rats (p=0.007). Simvastatin prevented the impairment in endothelial-dependent vasorelaxation induced by H/R, and reduced by half the increase in ALT and AST (p<0.05). Transcriptomics showed a marked upregulation of genes related to inflammatory response after H/R in cirrhotic livers, but not in controls, and this was blunted by simvastatin. In conclusion, H/R aggravates liver microvascular dysfunction in cirrhosis, and upregulates liver inflammatory pathways. This does not occur in control livers. Simvastatin prevented H/R-induced liver endothelial dysfunction, and attenuated liver injury and liver inflammatory response, suggesting that it might have potential for protecting the cirrhotic liver during bleeding complications. Overall design: Transcriptome analysis from CBDL (Common biliar duct ligation) rats submitted to a sham hemorrhage/resuscitation procedure (CBDLpS: n=5), CBDL rats submitted to hemorrhage/resuscitation (CBDLpH:n=6), CBDL rats pre-treated with simvastatin submitted to a sham hemorrhage/resuscitation procedure (CBDLpSS:n=5) and CBDL rats pre-treated with simvastatin submitted to hemorrhage/resuscitation (CBDLpSH:n=8). Also we included Controls submitted to a sham hemorrhage/resuscitation procedure (CONTROLS:n=5) and Controls submitted to hemorrhage/resuscitation (CONTROLH:n=6)

INSTRUMENT(S): [HT_Rat230_PM] Affymetrix HT RG-230 PM Array Plate

SUBMITTER: Juanjo Lozano  

PROVIDER: GSE84178 | GEO | 2016-12-22

SECONDARY ACCESSION(S): PRJNA328224

REPOSITORIES: GEO

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Publications

Simvastatin Attenuates Liver Injury in Rodents with Biliary Cirrhosis Submitted to Hemorrhage/Resuscitation.

Meireles Cintia Zimmermann CZ   Pasarin Marcos M   Lozano Juan Jose JJ   García-Calderó Héctor H   Gracia-Sancho Jordi J   García-Pagán Juan Carlos JC   Bosch Jaime J   Abraldes Juan G JG  

Shock (Augusta, Ga.) 20170301 3


Liver function deterioration is a major cause of death in variceal bleeding. The effects of bleeding on intrahepatic microvascular dysfunction, which contributes to liver injury in cirrhosis, are largely unknown. The aims of this study were to evaluate the impact of hemorrhage/resuscitation (H/R) on cirrhotic microcirculation, and whether simvastatin, a drug that improves liver microcirculation, has hepatoprotective effects. The study was performed in three groups of rats: controls, rats with bi  ...[more]

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