Fig. 2.

Increasing hypoxia amplifies VEGF production. a Each solid line represents the response of mRNA to step reduction of O₂ from normoxia (100% O₂) to a reduced O₂ level. The response is normalized to the mRNA baseline level at normoxia (baseline = 1). b and c Two simulation cases demonstrating that, by using different initial levels of biomolecules, either a “small” or “large” change in VEGF level (maximal changes of either 12-fold or 160-fold) can be elicited in response to the same mRNA response to hypoxia depicted in (a). Note the difference in the scale of y-axis. d Histogram depicting the distribution of VEGF response magnitude from 20,000 simulations in response to one step changes of O₂ level from 100 to 0.5%. e Decision tree showing that pAkt level is the sole factor dictating the magnitude to “large” (> 100) versus “small” (< 100) VEGF response