title: Liposome-mediated gene transfer of endothelial nitric oxide synthase to cirrhotic rat liver decreases intrahepatic vascular resistance.
abstract: OBJECTIVE
  Nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS) in sinusoidal endothelial cells is reduced in the injured liver and leads to intrahepatic portal hypertension. The present study evaluates the effects of liposome-mediated gene transfer of eNOS on the intrahepatic vascular resistance and portal venous pressure (PVP) in cirrhotic rats.
  
  
  METHODS
  Hepatic cirrhosis was induced in male Sprague-Dawley rats by intraperitoneal injection of carbon tetrachloride (CCl(4)), whereas the control normal rats were given the same dose of peanut oil. Plasmid eukaryotic expression vector (liposome-pcDNA3/eNOS) was injected into the portal vein of CCl(4) cirrhotic rats, whereas cirrhotic controls received the same dose of naked plasmid (liposome-pcDNA3) or Tris buffer, and control normal rats received the same dose of Tris buffer. Five days after gene transfer, the levels of eNOS mRNA and protein, NO production, PVP and the changes of hepatic intrahepatic vascular resistance were investigated.
  
  
  RESULTS
  Five days after eNOS gene transfer, the levels of eNOS mRNA, eNOS protein and NO production in cirrhotic rats increased remarkably, while hepatic vascular resistance and PVP decreased significantly in cirrhotic rats.
  
  
  CONCLUSIONS
  Liposome-mediated eNOS gene transfer via intraportal injection is feasible and the increase of intrahepatic eNOS leads to a marked decrease in introhepatic vascular resistance and PVP. These data indicate that intrahepatic eNOS plays an important role in the pathogenesis of portal hypertension and gene transfer of eNOS is a potential and novel therapy for portal hypertension.
authors: Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. zzq072@gmail.com
authors: Zhi-Qi
authors: ZQ
authors: Zhang
authors: Jiang-Feng
authors: JF
authors: Qiu
authors: Meng
authors: M
authors: Luo
authors: Yong-Wei
authors: YW
authors: Sun
authors: Gang
authors: G
authors: Zhao
authors: Wei
authors: W
authors: Chen
authors: Hua
authors: H
authors: Liu
authors: Zhi-Yong
authors: ZY
authors: Wu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D008081:Liposomes; D008099:Liver / Q000098:blood supply*; D008103:Liver Cirrhosis / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D017082:Portal Pressure / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000235:genetics / Q000502:physiology*
chemical_list: D008081:Liposomes; D052250:Nitric Oxide Synthase Type III