Angiogenesis is the formation of new blood vessels by sprouting from existing vessels. In order for new blood vessels to invade the surrounding tissue, the extracellular matrix must be degraded and subsequently remodeled. Fibulin (fbln)-5 (DANCE, EVEC) is an elastin and integrin binding extracellular matrix protein that is expressed strongly throughout the cardiovascular system during development and is re-expressed during vascular injury. Recently, an increase in the number of cutaneous blood vessels was observed on the posterior surface of the abdominal wall of the fbln5-/- mouse. In the present study, the role of fibulin-5 as an anti-angiogenic factor was investigated in vivo. The increase in vascular sprouting in the fbln5 -/- skin was confirmed to be significant by quantitative analysis. Using a well-established angiogenic model, polyvinyl alcohol (PVA) sponges were implanted subcutaneously in wild-type and fbln5-/- mice to determine the effect of the absence of fibulin-5 on fibrovascular invasion. Results showed no difference in fibroblast migration into the sponges from fbln5-/- and wild-type mice; however, PECAM-1 staining revealed a significant increase in microvascular invasion in sponges from fbln5 -/- mice. Sponges from fbln5-/- mice showed increased expression levels of VEGF and the angiopoietins relative to wild-type counterparts by quantitative RT-PCR. In addition, fibulin-5 inhibited bFGF induced neovascular invasion in Matrigel. In an ex vivo system, a lack of fibulin-5 stimulated vascular sprouting, and this response was blocked by the addition of exogenous fibulin-5. Taken together, these results indicate that fibulin-5 functions as an inhibitor of physiological angiogenesis and the absence of fibulin-5 results in an increase in vascularization.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.98807 |
| Date | January 2005 |
| Creators | Sullivan, Kaitlyn Marie. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Anatomy and Cell Biology.) |
| Rights | © Kaitlyn Marie Sullivan, 2005 |
| Relation | alephsysno: 002328939, proquestno: AAIMR24808, Theses scanned by UMI/ProQuest. |
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