Plasminogen activators augment endothelial cell organization in vitro by two distinct pathways

Area of Science:

• Cell Biology
• Biochemistry
• Angiogenesis Research

Background:

• Endothelial cell differentiation into capillary structures is vital for angiogenesis.
• Extracellular matrix proteases, particularly plasminogen activators (PAs), play a key role in this process.

Purpose of the Study:

• To investigate the specific roles of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) in endothelial cell morphogenesis.
• To elucidate the mechanisms by which PAs influence the formation of tubular structures in vitro.

Main Methods:

• Utilized an in vitro model of endothelial morphogenesis using human umbilical vein endothelial cells (HUVEC) cultured on Matrigel.
• Assessed the effects of PA inhibitors and matrix metalloproteinase inhibitors on tube network formation.
• Analyzed mRNA expression of uPA and the impact of a fucosylated uPA peptide on tube formation.

Main Results:

• Both uPA and tPA were detected in HUVEC cultures on Matrigel.
• Inhibitors of PAs and serine proteases significantly reduced tube network formation.
• A fucosylated uPA peptide, but not its defucosylated form, enhanced tube formation, suggesting dual mechanisms of action.

Conclusions:

• Plasminogen activators are essential for endothelial cell tube formation, influencing multiple events during morphogenesis.
• uPA enhances endothelial morphogenesis through both its proteolytic activity and interaction with the uPA receptor (uPAR).
• These findings suggest that PAs could facilitate angiogenesis in vivo.