title: Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam, Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Jun
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam, Korea.
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Catholic University Medical College, Seoul, Korea.
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainsville, FL, USA.
authors.forename: Seh Hoon
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Biomedical Science, CHA University, Seongnam, Korea.
authors.forename: Gi Jin
authors.initials: GJ
authors.lastname: Kim
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D002097:C-Reactive Protein / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006503:Hepatic Veins / Q000002:abnormalities; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008095:Lithocholic Acid / Q000494:pharmacology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism
chemical_list: D042501:Angiogenic Proteins; D034741:RNA, Small Interfering; D012709:Serum Albumin; D008095:Lithocholic Acid; D002097:C-Reactive Protein
keywords: Bile duct ligation; C-reactive protein; Hepatic disease; Primary biliary cirrhosis