Antiangiogenic Therapy for Diabetic Nephropathy

• Published in: BioMed research international Vol. 2017; no. 2017; pp. 1 - 12
• Main Authors: Wada, Jun, Sato, Yasufumi, Maeshima, Yohei, Tanabe, Katsuyuki
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2017; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Analysis; Angiogenesis; Angiogenesis Inhibitors; Animals; Antiangiogenics; Antibodies; Atherosclerosis; Blood pressure; Cell Cycle Proteins; Clinical medicine; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Diabetic nephropathy; Dosage and administration; Drug therapy; Endostatin; Endothelial cells; Endothelium; Humans; Immunological tolerance; Kidney diseases; Kidney Glomerulus - physiopathology; Kidneys; Kinases; Mice; Neovascularization, Pathologic; Nephropathy; Pathogenesis; Phosphorylation; Physiology; Proteinuria; Review; Rodents; Therapy; Thrombotic microangiopathy; Treatment outcome; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Japan
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2017/5724069

Angiogenesis has been shown to be a potential therapeutic target for early stages of diabetic nephropathy in a number of animal experiments. Vascular endothelial growth factor (VEGF) is the main mediator for abnormal angiogenesis in diabetic glomeruli. Although beneficial effects of anti-VEGF antibodies have previously been demonstrated in diabetic animal experiments, recent basic and clinical evidence has revealed that the blockade of VEGF signaling resulted in proteinuria and renal thrombotic microangiopathy, suggesting the importance of maintaining normal levels of VEGF in the kidneys. Therefore, antiangiogenic therapy for diabetic nephropathy should eliminate excessive glomerular angiogenic response without accelerating endothelial injury. Some endogenous antiangiogenic factors such as endostatin and tumstatin inhibit overactivation of endothelial cells but do not specifically block VEGF signaling. In addition, the novel endothelium-derived antiangiogenic factor vasohibin-1 enhances stress tolerance and survival of the endothelial cells, while inhibiting excess angiogenesis. These factors have been demonstrated to suppress albuminuria and glomerular alterations in a diabetic mouse model. Thus, antiangiogenic therapy with promising candidates will possibly improve renal prognosis in patients with early stages of diabetic nephropathy.