Mechanisms of Hypertension and Renal Injury During Vascular Endothelial Growth Factor Signaling Inhibition.

The recognition that angiogenesis is critical for tumor growth has stimulated the development of several agents that interfere with the process of angiogenesis. Of these agents, vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors have gained a prominent role in the treatment of a large variety of cancers. Along with their clinical introduction, treatment with VSP inhibitors appeared to be associated with the development of cardiovascular side effects, particularly hypertension, renal injury, cardiac dysfunction, thrombosis, and hemorrhage. When severe, these side effects are reason to discontinue VSP inhibitor treatment, obviously with repercussions for survival. In this review, we focus on mechanisms underlying the rise in blood pressure (BP) and kidney injury induced by VSP inhibitor treatment. Insight into the mechanisms of these side effects is not only of scientific interest, but may also provide a basis for their prevention with rational treatment. Because for a proportion of clinicians interested in hypertension the VEGF system is not common knowledge, we will start with a short description of this system and ways of its inhibition by pharmacological agents.