Endothelial cells decode VEGF-mediated Ca2+ signaling patterns to produce distinct functional responses

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Science Signaling  23 Feb 2016:
Vol. 9, Issue 416, pp. ra20
DOI: 10.1126/scisignal.aad3188

A calcium code for angiogenesis

During angiogenesis, a new blood vessel sprouts from an existing one, which requires that some endothelial cells migrate and provide guidance, and other cells proliferate and elongate the sprout. The proangiogenic factor VEGF stimulates both migration and proliferation through its receptor VEGFR2, and the amount of VEGFR2 signaling varies in the endothelial cells in the sprout. Noren et al. investigated how VEGF can specify different behaviors in genetically identical endothelial cells. High VEGF concentrations triggered a low, persistent calcium signal and stimulated migration. In contrast, low concentrations of VEGF triggered a repetitive spiking calcium waveform and stimulated proliferation. In sprouting blood vessels in developing zebrafish embryos, repetitive calcium spikes were detected in proliferating cells. Thus, VEGF triggers proliferation or migration in endothelial cells by stimulating different calcium signaling patterns.