Esm1 modulates endothelial tip cell behavior and vascular permeability by enhancing VEGF bioavailability

Area of Science:

• Vascular biology
• Cell signaling
• Immunology

Background:

• Endothelial cell-specific molecule 1 (Esm1) is a secreted protein implicated in angiogenesis and inflammation.
• Previous research lacked in vivo evidence for Esm1's function in these processes.

Purpose of the Study:

• To investigate the in vivo role of Esm1.
• To elucidate the molecular mechanisms underlying Esm1's function.

Main Methods:

• Generation and analysis of Esm1 knockout (Esm1(KO)) mice.
• Assessment of angiogenesis, vascular permeability, and leukocyte transmigration.
• Investigation of molecular signaling pathways, including Erk1/2 phosphorylation and VEGF-A interactions.

Main Results:

• Esm1 knockout mice displayed delayed vascular outgrowth and reduced filopodia extension, dependent on vascular endothelial growth factor A (VEGF-A).
• Esm1 deficiency led to decreased leukocyte transmigration and reduced VEGF-A-induced vascular permeability.
• Esm1 directly binds fibronectin, displacing VEGF-A165 and enhancing VEGF-A signaling.

Conclusions:

• Esm1 acts as both a target and modulator of VEGF signaling in endothelial cells.
• Esm1 plays a critical role in angiogenesis, inflammation, and vascular permeability.
• Esm1 represents a potential therapeutic target for vascular-related diseases.