uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Neovascularization is directed by tensile forces generated during tissue remodelling
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
(English)Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-92702OAI: oai:DiVA.org:uu-92702DiVA: diva2:165876
Available from: 2005-03-17 Created: 2005-03-17 Last updated: 2011-06-28Bibliographically approved
In thesis
1. Mechanisms of Tissue Vascularization
Open this publication in new window or tab >>Mechanisms of Tissue Vascularization
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Tissue neovascularization in postnatal life occurs during post-traumatic tissue healing, neoplastic growth and in the endometrium during the reproductive cycle of females. Although embryonic angiogenesis has been intensively studied, far less is known about tissue revascularization and vessel remodeling in adults due to methodological difficulties. In the current studies, we developed a novel in vivo model of neovascularization that is performed on the chicken chorioallantoic membrane (CAM). A provisional matrix placed on the CAM was vascularized in response to FGF-2. In order to distinguish new from pre-existing vessels, the matrix was separated from the CAM by a nylon grid. Techniques to visualize the three dimensional structure of vascular networks and a method for rapid and semi-automated quantification were developed. This novel model allowed us to study the effects of potential inhibitors of tissue vascularization and their effects on the pre-existing vasculature. We found that while fumagillin or inhibition of MEK and Src inhibited only neovascularization, addition of cortisol or wortmannin was toxic to pre-existing vessels.

The CAM model allowed intravital observations during extended periods of time, which together with immunohistochemical analysis revealed a novel mechanism of tissue vascularization. Tensional forces generated by myofibroblast-mediated contraction of the provisional matrix, induced and directed ingrowth of vascular tissue. During the initial stages of vascularization, the vascular network was recruited from the surrounding tissue through a non-angiogenic mechanism by elongation and enlargement of pre-existing vessels, which were moved as vascular loops with constant functional circulation. Ingrown vessels were remodeled, presumably through intussusception, fusion and pruning. The CAM model was validated by observations of neovascularization associated with healing of the injured mouse cornea.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 48 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 14
Pathology, vascularization, angiogenesis, granulation tissue, myofibroblast, wound healing, Patologi
National Category
Cell and Molecular Biology
urn:nbn:se:uu:diva-4819 (URN)91-554-6166-2 (ISBN)
Public defence
2005-04-08, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:00 (English)
Available from: 2005-03-17 Created: 2005-03-17 Last updated: 2009-05-13Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Gerwins, Pär
By organisation
Department of Genetics and PathologyDepartment of Medical Biochemistry and Microbiology

Search outside of DiVA

GoogleGoogle Scholar

Total: 157 hits
ReferencesLink to record
Permanent link

Direct link