Universität zu Köln

Schmidt, Annette (2003). The vascular development is modulated by endostatin and restin. PhD thesis, Universität zu Köln.

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Abstract

Endostatin and restin are proteolytic fragments of collagen XVIII and XV. They are described in literature as anti-angiogenic and consequently tumour-inhibitory proteins. The observation of endostatin and restin distribution as well as the distribution of their binding sites in the Embryoid Body (EB), in the embryo and during wound healing, suggests that they have an important role during vessel development. During vessel development of differentiated embryonic stem cells this two factors show both, an angiogenic and an anti-angiogenic effect by increasing endothelial proliferation and migration, processes which play an important role for vessel development and neovascularisation. On the other hand they induce endothelial apoptosis. The effect if endostatin and restin on neovascularisation and vessel development can therefore be described as an angio-modulatory. But endostatin and restin do not only influence endothelial proliferation, migration and apoptosis, they also influence endothelial morphogenesis by inducing a contraction or retraction of vessels. This phenomena was observed by vital-microscopy and deconvolution microscopy of embryonic vessels as well as during wound healing. The influence on morphogenesis leads to the question to which signaling pathways are involved. Especially for the morphogenesis our results imply that these processes are regulated by the VEGF signaling pathway or by molecules of the VEGF-signaling pathway. On cellulary level endostatin and restin show an influence of signaling molecules in endothelial cells. They lead to a dephosphorylation of the activated ERK1/2-kinase as well as to a down-regulation of the solouble Guanylate Cyclase (sGC) in a time course of 6 hours. The modulation of signaltransduction is induced by the protein phosphatase 2A (PP2A) because of the fact that inhibition of PP2A prevents dephosphorylation of activated ERK1/2-kinase and down-regulation of the sGC. The dephosphorylation of the activated ERK1/2-kinase is preventable by additional cGMP. Modulatory experiments by using cGMP and ODQ suggest that cGMP, under definitive conditions is able to stabilise the phosphorylation of the activated ERK1/2-kinase.

Item Type:	Thesis (PhD thesis)
Translated title:	Title Language Die vaskuläre Entwicklung wird durch Endostatin und Restin moduliert German The vascular development is modulated by endostatin and restin English
Creators:	Creators Email ORCID ORCID Put Code Schmidt, Annette Annette.Schmidt@uni-koeln.de UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-11416
Date:	2003
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Medicine > Anatomie > Institut I für Anatomie
Subjects:	Life sciences
Uncontrolled Keywords:	Keywords Language Endostatin , Restin , Angiogenese , Vaskulogenese German endostatin , restin , angiogenesis , vasculogenesis English
Date of oral exam:	2 November 2003
Referee:	Name Academic Title Addicks, Klaus Prof. Dr. med.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/1141