Figure 1.

VEGF is subject to complex regulation in response to acute and chronic hypoxia (as previously defined²¹). After 4 h of hypoxia (acute phase), p53 and HIF-1α induce VEGF transcription leading to a significant induction of mRNA. After 24 h (chronic phase) VEGF mRNA levels drop, but remain well above basal levels. In parallel time, E2F1 protein levels decrease in the acute phase and then normalize with extended hypoxia, while p53 protein levels were not observed to change.³ A role for E2F1 and Rb in the repression of VEGF is proposed, where E2F1 in the absence of Rb induces VEGF expression⁸