In some circumstances, excessive influx of VEGF-A (either exogenous for cells in vitro, or endogenous for ischemia models in vivo) may dysregulate intrinsic VEGFR balance of target cells and switch them to VEGFR1 expression or may upregulate soluble VEGFR1 expression that can operate as a negative feedback system, thereby undermining the entire positive effect of the treatment [22–24]. The gene discussed is KDR; the disease is ischemia.