Endothelial cells form the inner lining of vascular networks and maintain blood fluidity
by inhibiting blood coagulation and promoting blood clot dissolution (fibrinolysis).
Plasmin, the primary fibrinolytic enzyme, is generated by the cleavage of the plasma
protein, plasminogen, by its activator, tissue plasminogen activator (tPA). This reaction is
regulated by plasminogen receptors at the surface of the vascular endothelial cells.
Previous studies have identified the plasminogen receptor protein, S100A10 as a key
regulator of plasmin generation by cancer cells and macrophages. Here we examine the
role of S100A10 and its annexin A2 binding partner in endothelial cell function using a
homozygous S100A10-null mouse. Compared to wild-type mice, S100A10-null mice
displayed increased deposition of fibrin in the vasculature and reduced clearance of
batroxobin-induced vascular thrombi, suggesting a role for S100A10 in fibrinolysis in
vivo. Compared to WT cells, endothelial cells from S100A10-null mice demonstrated a
40% reduction in plasminogen binding and plasmin generation in vitro. Furthermore,
S100A10-deficient endothelial cells demonstrated impaired neovascularization of Matrigel plugs in vivo suggesting a role for S100A10 in angiogenesis. These results
establish an important role for S100A10 in the regulation of fibrinolysis and angiogenesis
in vivo, suggesting S100A10 plays a critical role in endothelial cell function.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:NSHD.ca#10222/15959 |
| Date | 13 October 2011 |
| Creators | Surette, Alexi P. |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_US |
| Detected Language | English |
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