Description

AIM The aim of this project is to study the role of placental growth factor (PLGF) in the development of portal hypertension and its complications, in the development of cirrhosis and steatosis/NASH. - We will focus on the role of PLGF in the formation of angiogenesis in the mesenterium, of collaterals (shunts) in the peripheral, splanchnic and pulmonary circulation, with also the study of initiating factors such as hypoxia (HIF pathway). The clinical complications of cirrhosis will be evaluated when induced in PLGF-/- mice. We will look if the clinical complications can be prevented (prevention studies) by administration of anti-angiogenic medication (anti-PLGF); if the formation of collaterals can be inhibited (see oral presentation C. Van Steenkiste), if pulmonary function can be influenced, if formation of ascites can be prevented and most importantly, if survival can be improved. As most patients in clinic are in the stage if cirrhosis and have overt PHT, we will look if each of these clinical complications are reversible with an anti-angiogenic treatment. - The relationship between HSC, causing fibrosis in chronic liver damage, and angiogenesis will be further studied. The effect of PLGF on HSC will be examined, but also the other way round, if HSC produce PLGF and induce angiogenesis. The use of PLGF-/- mice, anti-PLGF and recombinant PLGF will help us to study the role of PLGF in fibrosis. - In the mouse model of steatosis and NASH, the expression (protein/ mRNA) of VEGF and PLGF with their respective receptors will be examined at different time points in liver, lung and peritoneum. The effect of the development of steatosis, steatohepatitis and fibrosis on the microcirculation of peritoneum and liver (intravital microscopy and histology), on collateral formation, portal pressure and haemodynamics will be studied. In a second part, we will study the role of anti-angiogenic factors (anti-VEGF, anti-PLGF) in the development of steatohepatitis/fibrosis in NASH mouse models.
AcronymFWOAL494
StatusFinished
Effective start/end date1/01/0931/12/12

    Research areas

  • Fibrosis, Hepatic Stellate Cells, Histon (de)acetylation, Stellate cell activation, Liver Cell Transplantation, Portal hypertension, Sinusoidal Cells, Liver Sinusoidal Cells, Cell Biology, Cytoskeleton, Fat-Storing Cells, NASH / NAFLD, Intermediate Filaments, liver stem / progenitor cells, Flow Cytometry, Metabolic Syndrome, Chirrosis

    Flemish discipline codes

  • Electrical and electronic engineering
  • Basic sciences
  • Biological sciences

ID: 3293100