Clin Mol Hepatol.  2016 Sep;22(3):372-381. 10.3350/cmh.2016.0032.

Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation

• Jun JH
• Choi JH
• Bae SH
• Oh SH
• Kim GJ

• KMID: 2373138
• DOI: http://doi.org/10.3350/cmh.2016.0032

Abstract

BACKGROUND/AIMS
Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL).
METHODS
The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP.
RESULTS
The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP.
CONCLUSION
CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

Keyword

C-reactive protein; Bile duct ligation; Primary biliary cirrhosis; Hepatic disease

MeSH Terms

Angiogenic Proteins/genetics/metabolism
Animals
Bile Ducts/surgery
C-Reactive Protein/*analysis/genetics/metabolism
Cells, Cultured
Disease Models, Animal
Hepatic Veins/abnormalities
Hepatocytes/cytology/metabolism
Human Umbilical Vein Endothelial Cells
Humans
Lithocholic Acid/pharmacology
Liver/metabolism/pathology
Liver Cirrhosis/etiology
Liver Diseases/metabolism/*pathology
Male
Microscopy, Fluorescence
Mitochondria/drug effects/metabolism
RNA Interference
RNA, Small Interfering/metabolism
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Serum Albumin/genetics/metabolism
Angiogenic Proteins
C-Reactive Protein
Lithocholic Acid
RNA, Small Interfering
Serum Albumin