title: Immunolocalization of VEGF A and its receptors, VEGFR1 and VEGFR2, in the liver from patients with biliary atresia.
abstract: In biliary atresia (BA), a cholangiopathy of elusive etiology invariably leads to cirrhosis, and a disturbed angiogenesis may be involved. We evaluated the hepatobiliary immunolocalization of vascular endothelial growth factor (VEGF) A, VEGF receptor 1 (R1), and R2 in BA. We analyzed biopsies obtained at portoenterostomy from infants with BA (n=52), including embryonic (n=14) and perinatal (n=38) types. Controls were infants with intrahepatic cholestasis (IC; n=7). In BA, VEGF A immunolocalization was also evaluated in explants (n=33) and at the porta hepatis (n=16). We morphometrically assessed the percentage of CK7 (PCK7) positivity in BA and the ratio medial layer thickness/luminal diameter in hepatic artery branches in BA and IC. We found that arteries were more frequently positive for VEGF A in BA at portoenterostomy (P=0.006) than in other groups. In explants, VEGF A immunolocalization was mainly lobular (P<0.001). VEGFR2 was less frequently positive in BA than IC in bile ducts (P=0.023) and hepatocytes (P=0.011). A higher PCK7 positivity was associated with arterial (P<0.001) and biliary (P=0.040) VEGF A positivity. PCK7 was correlated with biliary (P=0.031), arterial (P=0.031), and hepatocytic (P=0.032) VEGF A positivity in BA at portoenterostomy. VEGF A was positive in arteries and bile ducts at the porta hepatis mainly in the perinatal BA type (P=0.013). Biliary (P=0.016) and arterial (P=0.044) VEGF A positivity were associated with higher ratio medial layer thickness/luminal diameter values. Our findings suggest that hypoxia/ischemia affects the portal structures in BA at portoenterostomy, beginning at the porta hepatis, and it is associated both with the extent of biliary proliferation and medial layer thickening.
authors.affiliation: Laboratório Experimental de Hepatologia e Gastrenterologia do Centro de Pesquisas do Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Patrícia Turnes
authors.initials: PT
authors.lastname: Edom
authors.forename: Luise
authors.initials: L
authors.lastname: Meurer
authors.forename: Themis Reverbel
authors.initials: TR
authors.lastname: da Silveira
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
authors.forename: Jorge Luiz
authors.initials: JL
authors.lastname: dos Santos
mesh_terms: D001656:Biliary Atresia / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006499:Hepatic Artery / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D053552:Keratin-7 / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008853:Microscopy; D011171:Portoenterostomy, Hepatic; D017540:Tunica Media / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D053552:Keratin-7; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2