Investigating transient and prolonged VEGF signaling through regulation of intracellular calcium

Abstract

Vascular endothelial growth factor (VEGF) is a key regulator of vascular structure and function and has a profound influence on both angiogenesis and vascular permeability. While several signaling pathways have been shown to transmit information from VEGF receptors, recent attention has highlighted a role for intracellular calcium in regulating EC proliferation, migration, and the production of vasoactive factors like nitric oxide. Here we present a mathematical model describing the regulation of intracellular calcium via VEGF. The model is able to reproduce several of the interesting dynamics normally associated with VEGF stimulation of calcium release. These include both the initial rapid transient increases in intracellular calcium and a biphasic response leading to more prolonged and increased calcium levels. Results from the model were validated through in vitro experiments and provide insight into how VEGF can regulate both immediate and extended signaling to endothelial cells. This work was supported by NIH grants R01 HL79653 and R33 HL87351.