Figure 7.

Putative mechanisms involving ET-1 system whereby MPs released under VEGFi treatment causes endothelial cell dysfunction. VEGF/VEGFR inhibition causes an increase in ECMPs release which suggests an endothelial injury. In addition to carry ET-1, MPs induce endothelial cells damage by increasing ET-1 production, inflammation and ROS production through ETA and ETB activation but also by down-regulating eNOS/NO signalling. The dysregulation of endothelial cell function induced by MPs may induce vascular tone alterations and endothelial dysfunction, and may explain, at least partially, molecular mechanisms underlying VEGFi-associated hypertension.