Shear Stress and VE-Cadherin

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Molecular Biology

Background:

• Vascular fusion is crucial for vessel enlargement during development.
• The molecular mechanisms driving postnatal vascular fusion remain largely unknown.
• Previous studies linked low shear stress and DAPT treatment to hyperfused vascular plexuses.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying vascular fusion.
• To investigate the role of vascular endothelial-cadherin (VEC) phosphorylation in vascular fusion.

Main Methods:

• Investigated VEC phosphorylation in response to low shear stress and DAPT treatment.
• Examined the effect of shear stress on VEC-associated phosphatases.
• Assessed the impact of Src inhibition and Moesin localization on vascular fusion.

Main Results:

• DAPT treatment and low shear stress increase VEC phosphorylation independently of Notch signaling.
• Increased shear stress promotes the association of vascular endothelial-protein tyrosine phosphatase with VEC, reducing phosphorylation.
• Src inhibition prevents VEC phosphorylation and rescues hyperfusion; Moesin relocalizes to cell membranes during fusion.

Conclusions:

• VEC phosphorylation is a key molecular event in vascular fusion during remodeling.
• Modulating VEC phosphorylation offers a potential therapeutic target for vascular diseases.