Vascular endothelial growth factor increases microvascular permeability via a Ca(2+)-dependent pathway

Area of Science:

• Physiology
• Cell Biology
• Vascular Biology

Background:

• Vascular endothelial growth factor (VEGF) is crucial for angiogenesis and vascular permeability.
• The precise mechanisms by which VEGF modulates microvascular permeability are still under investigation.
• Calcium influx into endothelial cells is a known regulator of vascular tone and permeability.

Purpose of the Study:

• To test the hypothesis that VEGF increases microvascular permeability by promoting calcium influx into endothelial cells.
• To elucidate the role of calcium signaling in VEGF-induced changes in microvascular hydraulic conductivity.

Main Methods:

• Isolated perfused frog mesenteric microvessels were used to measure microvessel hydraulic conductivity (Lp).
• VEGF was perfused under conditions designed to attenuate or modulate calcium influx (e.g., depolarization, nickel ion addition).
• Intracellular calcium concentrations in endothelial cells were measured using fura 2 fluorescence.

Main Results:

• VEGF significantly increased microvessel hydraulic conductivity (Lp).
• The increase in Lp induced by VEGF was attenuated under conditions of reduced calcium influx (depolarization, nickel ions).
• VEGF elevated intracellular calcium concentration in endothelial cells.

Conclusions:

• VEGF increases microvascular permeability by enhancing calcium influx into endothelial cells.
• Calcium signaling is a key mediator of VEGF's effect on microvascular hydraulic conductivity.
• These findings provide mechanistic insight into VEGF-driven vascular permeability.