Year: 2011
Type: dissertation
Abstract: ABSTRACT\nAngiogenesis, the process by which new vessels sprout from pre-existing\nvessels, is fundamental to development, tissue growth and repair. The main\naim of this thesis was to investigate the role of microglia on angiogenesis.\nWe adapted the rat ex vivo/in vitro aortic ring model to the mouse in a 3-D\nculture system. In paper I, we show that ablation of microglia in the retina\nleads to a poorly developed vascular network. The aortic ring model,\nsupplied with microglia, demonstrated that microglia have a direct positive\neffect on angiogenic sprouting. The angiogenic effect was mediated by\nsoluble factor/factors, and cell-cell contacts were not required. We also\nshow that the microglia-derived angiogenic factor(s) is distinct from\nvascular endothelial growth factor-A. Moreover, the sprouting aortic ring\ninduces oriented migration of microglia towards the aortic ring. In paper II,\nwe analysed the microglia transcriptome. We found that microglia express\nknown activators and inhibitors of angiogenesis that might have a role in\nretinal blood vessel development. The aortic ring system was also used as a\ncomplement to in vivo analyses to address the function of sphingosine-1-\nphosphate receptor 1 (S1P1) on angiogenesis (paper III). The results\nindicate that S1P1 is required within endothelial cells to counteract VEGFA-\nsignalling and prevent endothelial hyper-sprouting. In paper IV,\nexpression of green fluorescent protein in endothelial/hematopoietic cells\nusing Tie2-Cre was used to mark transplanted bone marrow-derived cells.\nThe study aimed to address if grafted bone marrow derived cells can\ndifferentiate into pancreatic β-cells in mice. The major part of the thesis\nconcerns the establishment and use of the mouse aortic ring as a model for\nangiogenesis. Importantly, application of the system enabled us to identify\na direct positive effect of microglia on angiogenesis and to test putative\nmodifiers. This could be further pursued by microarray analyses. The\npresented work might therefore provide a platform for the identification of\nmolecules that regulate angiogenesis.\nKey words: microglia, angiogenesis, aortic ring.\nISBN: 978-91-628-8285-3
Author: Simin Rymo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: Karolinska Institutet
OpenAlex ID: W2124964679