Immunoregulation mechanism of VEGF signaling pathway inhibitors and its efficacy on the kidney

Abstract

Angiogenesis and immunosuppression are closely related pathophysiologic processes. Widely prescribed in malignant tumor and proliferative retinal lesions, VEGF signaling pathway inhibitors may cause hypertension and renal injury in some patients, presenting with proteinuria, nephrotic syndrome, renal failure and thrombotic microangiopathy. VEGF signaling pathway inhibitors block the action of both VEGF-A and VEGF-C. However, VEGF-A and VEGF-C produced by podocytes are vital to maintain the physiological function of glomerular endothelial cells and podocytes. There is still no effective treatment for kidney disease associated with VEGF signaling pathway inhibitors and some patients have progressive renal failure even after withdrawal of the drug. Recent studies reveal that blocking of VEGF-A and VEGF-C can activate CD4 ⁺and CD8⁺ T cells, augment antigen-presenting function of dendritic cells, enhance cytotoxicity of macrophages and initiate complement cascade activation. VEGF and VEGFR are expressed in immune cells, which are involved in the immunosuppression and cross-talk among immune cells. This review summarizes the expression and function of VEGF-A and VEGF-C in the kidney. The current immunoregulation mechanisms of VEGF signaling pathway inhibitors are reviewed. Finally, combinate strategies are summarized to highlight the proposal for VEGF signaling pathway inhibitors.

Keywords: Immune mechanism; Kidney disease; Therapy; VEGF signaling pathway inhibitors.