Uncoupling of VEGF with Endothelial NO as a Potential Mechanism for Abnormal Angiogenesis in the Diabetic Nephropathy

Figure 1

Central role of NO in regulating VEGF system in endothelial cells. In endothelium, VEGFR1 contributes to NO production whereas endothelial cell proliferation is regulated by VEGFR2. VEGFR1 is also expressed in macrophage as well as VSMC. In the normal setting, endothelial cells produce NO, which negatively regulates endothelial cell proliferation, macrophage migration, and VSMC activation to maintain the well balanced vascular integrity. In contrast, endothelial NO bioavailability is reduced in certain physiological conditions, such as diabetes. In the case that NO bioavailability is reduced in endothelium, a compensatory increase in VEGF expression as well as a disruption of negative regulation in vascular system in response to VEGF occurs. As a consequence, VEGF engages VEGFR2 to enhance endothelial cell proliferation while VEGFR1 on macrophage and VSMC can be activated to induce vascular injury.