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This Article Full Text Full Text (PDF) All Versions of this Article: 291/2/G307    most recent 00507.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Gaudio, E. Articles by Alpini, G. Search for Related Content PubMed PubMed Citation Articles by Gaudio, E. Articles by Alpini, G.

LIVER AND BILIARY TRACT

Administration of r-VEGF-A prevents hepatic artery ligation-induced bile duct damage in bile duct ligated rats

¹Central Texas Veterans Health Care System, ²Departments of Medicine and ⁴Systems Biology and Translation Medicine, ³Division of Research and Education, Scott and White Hospital and Texas A&M University System Health Science Center, College of Medicine, Temple, Texas; ⁵Department of Gastroenterology, Tohoku University School of Med, Aobaku, Sendai, Japan; Divisions of ⁶Gastroenterology and ⁷Anatomy, University La Sapienza, Rome, Italy; and ⁸Department Experimental Medicine, University of L’Aquila, L’Aquila, Italy

Submitted 27 October 2005 ; accepted in final form 20 March 2006

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.

cAMP; ductal secretion; intrahepatic biliary epithelium; mitosis; microcirculation; secretin