FIG. 1.
Abnormal angiogenesis in diabetic nephropathy. A: Extraglomerular neovascularization (black arrows) are found in type 2 diabetic patients. Reprinted with permission from ref. 6. B: Similarly, immunohistochemistry for CD34, a marker for endothelial cells, indicates the normal glomerular capillary pattern (brown) in nondiabetic C57BL6 mice (a). Alternatively, abnormal capillary formation is observed around glomerulus in diabetic mice lacking endothelial nitric oxide synthase (b), resembling abnormal angiogenesis in human diabetic nephropathy. Reprinted with permission from ref. 33. C: The association of abnormal angiogenesis with VEGF expression in diabetic eNOSKO mice. In contrast to glomerulus in normal mice, glomerular endothelial staining is increased along with VEGF expression. However, hydralazine treatment attenuates the increase in glomerular capillary number and VEGF expression in diabetic eNOSKO mice. D: Glomerular filtrate and atubular glomerulus in diabetic eNOSKO mice. Glomerular filtrates are delivered to the outside of the glomerulus (arrow in a) and spread to the glomerulotubular junction (arrows in a and b). This filtrate may lead to a disconnection between glomerulus and proximal tubules (b). Ballooning of Bowman's capsule is observed in c. Glomeurlar filtrate can be observed outside of Bowman's capsule in the tubular pole, where the proximal tubulus is completely disconnected from the glomerulus. Bar = 40 μm. (A high-quality digital representation of this figure is available in the online issue.)