Hypoxic induction of the hypoxia-inducible factor is mediated via the adaptor protein Shc in endothelial cells.

Tyrosine kinase cascades may play a role in the hypoxic regulation of hypoxia-inducible factor (HIF)-1. We investigated the role of tyrosine kinase phosphorylation and of the Shc/Ras cascade on hypoxic HIF-1 stabilization. Exposure of human umbilical vein endothelial cells to hypoxia results in HIF protein stabilization as early as 10 minutes, with a maximum at 3 hours, and also in Shc tyrosine phosphorylation, with a maximum at 10 minutes.

Dephosphorylation of endothelial nitric oxide synthase contributes to the anti-angiogenic effects of endostatin.

Endostatin is an anti-angiogenic factor that inhibits endothelial cell (EC) migration and induces EC apoptosis. Because nitric oxide (NO) plays a key role in vascular endothelial growth factor (VEGF)-induced angiogenesis, we hypothesized that endostatin interferes with the activation of the endothelial NO synthase (eNOS). Human recombinant endostatin significantly reduced VEGF-induced NO-release, which suggests that endostatin inhibits eNOS activation.

Shear stress-induced endothelial cell migration involves integrin signaling via the fibronectin receptor subunits alpha(5) and beta(1).

Endothelial cell (EC) migration is required for angiogenesis, neovascularization, and reendothelialization. Integrins, known as alphabeta-heterodimeric cell-surface receptors, regulate cell migration and are essential for mechanotransduction of hemodynamic forces. Therefore, we investigated the effect of shear stress on EC migration and the contribution of the integrins and integrin-dependent signaling pathways in a scratched-wound assay.