VEGFA and hypertensive disorder: In addition, blocking VEGF could also trigger endothelial dysfunction and influenced VEGF-associated vascular pathways (down-regulating vasodilatory pathways such as nitric oxide and prostaglandin I2, and up-regulating vasoconstriction pathway such as endothelin-1), resulting in increased afterload and hypertension (Fukasawa et al., 2014).