Administration of r-VEGF-A prevents hepatic artery ligation-induced bile duct damage in bile duct ligated rats.
The hepatic artery, through the peribiliary plexus, nourishes the intrahepatic biliary tree. During obstructive cholestasis, the nutritional demands of intrahepatic bile ducts are increased as a consequence of enhanced proliferation; in fact, the peribiliary plexus (PBP) displays adaptive expansion. The effects of hepatic artery ligation (HAL) on cholangiocyte functions during cholestasis are unknown, although ischemic lesions of the biliary tree complicate the course of transplanted livers and are encountered in cholangiopathies. We evaluated the effects of HAL on cholangiocyte functions in experimental cholestasis induced by bile duct ligation (BDL). By using BDL and BDL + HAL rats or BDL + HAL rats treated with recombinant-vascular endothelial growth factor-A (r-VEGF-A) for 1 wk, we evaluated liver morphology, the degree of portal inflammation and periductular fibrosis, microcirculation, cholangiocyte apoptosis, proliferation, and secretion. Microcirculation was evaluated using a scanning electron microscopy vascular corrosion cast technique. HAL induced in BDL rats 1) the disappearance of the PBP, 2) increased apoptosis and impaired cholangiocyte proliferation and secretin-stimulated ductal secretion, and 3) decreased cholangiocyte VEGF secretion. The effects of HAL on the PBP and cholangiocyte functions were prevented by r-VEGF-A, which, by maintaining the integrity of the PBP and cholangiocyte proliferation, prevents damage of bile ducts following ischemic injury.
Division of Anatomy, University La Sapienza, Rome, Italy.
Eugenio
E
Gaudio
Barbara
B
Barbaro
Domenico
D
Alvaro
Shannon
S
Glaser
Heather
H
Francis
Antonio
A
Franchitto
Paolo
P
Onori
Yoshiyuki
Y
Ueno
Marco
M
Marzioni
Giammarco
G
Fava
Julie
J
Venter
Ramona
R
Reichenbach
Ryun
R
Summers
Gianfranco
G
Alpini
D000818:Animals; D001652:Bile Ducts / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D002779:Cholestasis / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006499:Hepatic Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008026:Ligation; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
D042461:Vascular Endothelial Growth Factor A