Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schwabl, P; Payer, BA; Grahovac, J; Klein, S; Horvatits, T; Mitterhauser, M; Stift, J; Boucher, Y; Trebicka, J; Trauner, M; Angermayr, B; Fuhrmann, V; Reiberger, T; Peck-Radosavljevic, M.
Pioglitazone decreases portosystemic shunting by modulating inflammation and angiogenesis in cirrhotic and non-cirrhotic portal hypertensive rats.
J Hepatol. 2014; 60(6): 1135-1142.
Doi: 10.1016/j.jhep.2014.01.025
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Trauner Michael
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- Abstract:
- Development of the portal-hypertensive syndrome is mediated by splanchnic inflammation and neoangiogenesis. Since peroxisome proliferator-activated receptor gamma (PPARγ) agonists like pioglitazone (PIO) regulate inflammatory response and inhibit angiogenesis in endothelial cells, we evaluated PIO as treatment for experimental portal hypertension. PIO (10 mg/kg) or vehicle (VEH) was administered from day 21-28 after bile duct ligation (BDL), from day 0-7 after partial portal vein ligation (PPVL) or sham-operation (SO), respectively. After treatment, systemic hemodynamics, splanchnic blood flow (SMABF), portal pressure (PP), and portosystemic shunting (PSS) were assessed. Splanchnic and hepatic tissues were analyzed for angiogenic and inflammatory markers. BDL and PPVL showed significantly increased PP, SMABF, and PSS compared to SO-VEH rats. While PIO treatment did not decrease PP or SMABF, PSS was significantly reduced both in cirrhotic (BDL-VEH: 71% to BDL-PIO: 41%; p<0.001) and non-cirrhotic (PPVL-VEH: 62% to PPVL-PIO: 40%; p=0.041) rats. PIO (10 μM, in vitro) inhibited endothelial cell migration and significantly increased PPARγ activity in vivo. In BDL rats, PIO decreased hepatic mRNA levels of PPARγ (p=0.01) and PlGF (p=0.071), and splanchnic mRNA expression of PPARγ (p=0.017), PDGFβ (p=0.053) and TNFα (p=0.075). Accordingly, splanchnic protein expression of PPARγ (p=0.032), VEGFR2 (p=0.035), CD31 (p=0.060) and PDGFβ (p=0.066) were lower in BDL-PIO vs. BDL-VEH animals. In PPVL rats, PIO treatment decreased splanchnic gene expression of Ang2 (-12.4 fold), eNOS (-9.3 fold), PDGF (-7.0 fold), PlGF (-11.9 fold), TGFb (-8.3 fold), VEGF-A (-11.3 fold), VEGFR1 (-5.9 fold), IL1b (-14.4 fold), and IL6 (-9.6 fold). Pioglitazone treatment decreases portosystemic shunting via modulation of splanchnic inflammation and neoangiogenesis. Pioglitazone should be assessed for potential beneficial effects in patients with portosystemic collaterals due to portal hypertension. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Movement - drug effects Cell Movement - physiology
- Disease Models, Animal -
- Hemodynamics - drug effects Hemodynamics - physiology
- Human Umbilical Vein Endothelial Cells -
- Humans -
- Hypertension, Portal - drug therapy Hypertension, Portal - immunology Hypertension, Portal - physiopathology
- Hypoglycemic Agents - pharmacology
- Inflammation - drug therapy Inflammation - immunology Inflammation - physiopathology
- Liver Circulation - drug effects Liver Circulation - physiology
- Liver Cirrhosis, Experimental - drug therapy Liver Cirrhosis, Experimental - immunology Liver Cirrhosis, Experimental - physiopathology
- Male -
- Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - immunology Neovascularization, Pathologic - physiopathology
- PPAR gamma - metabolism
- Portal Pressure - drug effects Portal Pressure - physiology
- Rats, Sprague-Dawley -
- Splanchnic Circulation - drug effects Splanchnic Circulation - immunology Splanchnic Circulation - physiology
- Thiazolidinediones - pharmacology
- Find related publications in this database (Keywords)
- Angiogenesis
- Inflammation
- Portal hypertension
- BDL
- PPVL
- Pioglitazone
- Portosystemic shunting
- PPAR gamma