Tie2 Pathway - A Key Regulator of Vascular Stability
The Tie2 pathway was discovered 20 years ago. Since that time considerable scientific evidence has established active Tie2 as a key regulator of vascular stability.
Tie2 is activated by the binding of the ligand, angiopoietin-1 (Angpt1). In the retina, Angpt1 is predominantly produced by pericytes that surround retinal capillaries. Activated Tie2 is responsible for the maintenance of vascular stability and quiescence in normal, healthy vasculature.
Tie2 activity is downregulated by two mechanisms: deactivation of active Tie2 by vascular endothelial protein tyrosine phosphatase (VE-PTP) and binding of the non-activating ligand angiopoietin-2 (Angpt2).
Both VE-PTP and Angpt2 are upregulated by hypoxia and tissue ischemia, diabetes and hypertension conditions that are characterized by endothelial dysfunction and vascular destabilization.
VE-PTP deactivates active Tie2 on the intracellular side of the receptor, acting as an "off-switch".
Angpt2 binds to and occupies the Tie2 receptor without activation. This action competitively inhibits Angpt1 activity on the Tie2 receptor.