Liposome-mediated gene transfer of endothelial nitric oxide synthase to cirrhotic rat liver decreases intrahepatic vascular resistance.
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.
Zhang
Zhi-Qi
ZQ
Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. zzq072@gmail.com
Qiu
Jiang-Feng
JF
Luo
Meng
M
Sun
Yong-Wei
YW
Zhao
Gang
G
Chen
Wei
W
Liu
Hua
H
Wu
Zhi-Yong
ZY
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*
D008081:Liposomes; D052250:Nitric Oxide Synthase Type III