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Role of vascular endothelial growth factor in the pathophysiology of non-alcoholic steatohepatitis in two mice models

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Coulon, Stéphanie [U Ghent] Legry, Vanessa [UCL] Heindryckx, Femke [U Ghent] Van Steenkiste, Christophe [U Ghent] Casteleyn, Christophe [U GhentU of Antwerpen] Libbrecht, Louis [UCL] Leclercq, Isabelle [UCL] Geerts, Anja [UGhent]

The pathophysiology of non-alcoholic steatohepatitis (NASH) should be approached as a multifactorial process. In several stages of NASH, a link between disease progression and hepatic microvasculature changes can be made. In this study we investigated the role of angiogenesis in two mice models for NASH, and the effect of a preventive and therapeutic anti-angiogenic treatment in a diet-induced mouse model for NASH. Protein and RNA levels of angiogenic and inflammatory factors were significantly up-regulated in the liver of C56BL/6 and db/db mice with NASH at different time-points. To examine the effect of angiogenic factors on the disease progression of NASH, a prevention and treatment study was set-up, blocking the placental growth factor (PlGF) or vascular endothelial growth factor receptor 2 (VEGFR2). Our study showed that αVEGFR2 treatment prevents the progression of NASH by attenuating steatosis and inflammation, both in a preventive and therapeutic set-up. Thereby confirming the hypothesis that angiogenic factors play an early role in the disease progression from steatosis to NASH. Anti-PlGF (αPlGF) did not significantly improve liver histology. Vascular corrosion casting showed a more disrupted liver vasculature in mice with NASH compared to controls. Treatment with αVEGFR2 showed an improvement of the liver vasculature. Moreover, fat-laden primary hepatocytes treated with αVEGFR2 stored significantly less lipids. Conclusion:Our results demonstrate that there is an increased expression of angiogenic factors in the liver in different mice models for NASH. We found that VEGFR2 blockage attenuates steatosis and inlammation in a diet-induced mouse model for NASH in a preventive and therapeutic setting. Our findings warrant further investigation of the role of angiogenesis in the pathophysiology in NASH.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2013
Language Anglais
Journal information "Hepatology" - Vol. 57, no. 5, p. 1793-1805 (2013)
Peer reviewed yes
Publisher JohnWiley & Sons, Inc. ((United States) Hoboken, NY)
issn 0270-9139
e-issn 1527-3350
Publication status Publié
Affiliation UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie
Links
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Bibliographic reference Coulon, Stéphanie ; Legry, Vanessa ; Heindryckx, Femke ; Van Steenkiste, Christophe ; Casteleyn, Christophe ; et. al. Role of vascular endothelial growth factor in the pathophysiology of non-alcoholic steatohepatitis in two mice models. In: Hepatology, Vol. 57, no. 5, p. 1793-1805 (2013)
Permanent URL http://hdl.handle.net/2078.1/121960