Angiogenesis in liver fibrosis

Amirah Adlia

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Angiogenesis emerges in parallel with liver fibrosis, but it is still unclear whether angiogenesis is a defense mechanism of the body in response to fibrosis, or whether it aggravates the fibrotic condition. In this thesis, Amirah Adlia applied different approaches to elucidate the role of angiogenesis in fibrosis. She started by targeting the anti-angiogenic cytokine, interferon alpha (IFNα), to the hepatocytes in fibrotic livers with the aim to study the role of hepatocytes in fibrosis-associated angiogenesis. It was shown that both IFNα and targeted IFNα inhibited angiogenesis, but did not affect fibrosis development in vivo. This was supported by another approach in this thesis using liver slices to elucidate the role of angiogenesis in the development of fibrosis. The pro-angiogenic factor VEGF-A had no direct stimulating effect on liver fibrotic genes. In addition, no correlation was found between factors of these two pathological processes. Thus, based on these studies it was concluded that angiogenesis is present in fibrotic livers but does not influence fibrosis progression in the liver.

In addition, the liver slice studies yielded a new ex vivo angiogenesis model to study in particular fibrosis-associated angiogenesis. To date, most of the angiogenesis models were developed for cancer, and there is the lack of specific assay that represents this pathological condition in liver fibrosis. The results indicated that studies using precision-cut slices offer a promising ex vivo model to investigate disease-associated angiogenesis, which will contribute to the reduction, replacement, and refinement of animal experiments.
Originele taal-2English
KwalificatieDoctor of Philosophy
Toekennende instantie
  • Rijksuniversiteit Groningen
Begeleider(s)/adviseur
  • Groothuis, Geny, Supervisor
  • Poelstra, Klaas, Supervisor
  • Olinga, Peter, Beoordelingscommissie
  • Molema, Ingrid, Beoordelingscommissie
  • Elferink, Ronald P. J. Oude, Beoordelingscommissie, Externe Persoon
Datum van toekenning20-feb-2017
Plaats van publicatie[Groningen]
Uitgever
Gedrukte ISBN's978-90-367-9519-7
Elektronische ISBN's978-90-367-9518-0
StatusPublished - 2017

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