title: Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride-induced rat liver cirrhotic model.
abstract: OBJECTIVE
  In cirrhosis, sinusoidal endothelial cell injury results in increased endothelin-1 (ET-1) and decreased nitric oxide synthase (NOS) activity, leading to portal hypertension. However, the effects of transplanted endothelial progenitor cells (EPCs) on the cirrhotic liver have not yet been clarified. We investigated whether EPC transplantation reduces portal hypertension.
  
  
  METHODS
  Cirrhotic rats were created by the administration of carbon tetrachloride (CCl(4) ) twice weekly for 10 weeks. From week 7, rat bone marrow-derived EPCs were injected via the tail vein in this model once a week for 4 weeks. Endothelial NOS (eNOS), vascular endothelial growth factor (VEGF) and caveolin expressions were examined by Western blots. Hepatic tissue ET-1 was measured by a radioimmunoassay (RIA). Portal venous pressure, mean aortic pressure, and hepatic blood flow were measured.
  
  
  RESULTS
  Endothelial progenitor cell transplantation reduced liver fibrosis, α-smooth muscle actin-positive cells, caveolin expression, ET-1 concentration and portal venous pressure. EPC transplantation increased hepatic blood flow, protein levels of eNOS and VEGF. Immunohistochemical analyses of eNOS and isolectin B4 demonstrated that the livers of EPC-transplanted animals had markedly increased vascular density, suggesting reconstitution of sinusoidal blood vessels with endothelium.
  
  
  CONCLUSIONS
  Transplantation of EPCs ameliorates vascular dysfunction and portal hypertension, suggesting this treatment may provide a new approach in the therapy of portal hypertension with liver cirrhosis.
authors: Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors: Masaharu
authors: M
authors: Sakamoto
authors: Toru
authors: T
authors: Nakamura
authors: Takuji
authors: T
authors: Torimura
authors: Hideki
authors: H
authors: Iwamoto
authors: Hiroshi
authors: H
authors: Masuda
authors: Hironori
authors: H
authors: Koga
authors: Mitsuhiko
authors: M
authors: Abe
authors: Osamu
authors: O
authors: Hashimoto
authors: Takato
authors: T
authors: Ueno
authors: Michio
authors: M
authors: Sata
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology*; D002251:Carbon Tetrachloride; D022461:Caveolins / Q000378:metabolism; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000502:physiology / Q000637:transplantation*; D019332:Endothelin-1 / Q000378:metabolism; D004727:Endothelium / Q000201:enzymology / Q000378:metabolism*; D006975:Hypertension, Portal / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D008102:Liver Circulation; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017082:Portal Pressure; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D022461:Caveolins; D019332:Endothelin-1; D042461:Vascular Endothelial Growth Factor A; D002251:Carbon Tetrachloride; D052250:Nitric Oxide Synthase Type III