The endothelial nitric oxide synthase-deficient (eNOS<sup>-/-</sup>) <i>db</i>/<i>db</i> mouse is an appropriate and valuable model to study mechanisms in the development of diabetic nephropathy because of the similarities of the features of diabetic kidney disease in this model to those in humans.
Finally, increased phospho-histone H3Ser10 levels were observed in the kidneys of diabetic endothelial nitric oxide synthase knockout mice and in the glomeruli of humans with diabetic kidney disease.
We examined whether BMS002, a novel dual LPAR1 and LPAR3 antagonist, affects development of DN in endothelial nitric oxide synthase-knockout <i>db/db</i> mice.
The results revealed that variations of ACE and eNOS gene had association with DN, which indicated ACE and eNOS gene may play an important role in pathogenesis of DN in Northern Chinese Han population.
Overall, although there is some evidence of association between NOS type III 4b/a polymorphism and DN in Asian population, the more reliable findings need further and more rigorous, prospective and high-quality studies.
To investigate the association of functional single nucleotide polymorphisms (SNPs) of the endothelial nitric oxide synthase gene (eNOS) gene (T-786C, G894T) and one variable number tandem repeat polymorphism (aa 27VNTR bb) with reno-protective response to angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) therapy in North Indian type 2 diabetic mellitus (T2DM) subjects with cases having diabetic nephropathy (DN) and controls without DN.
The aim of this study was to evaluate the association of three polymorphisms of the eNOS gene (894G>T, -786T>C, and 27-bp-VNTR) with the risk of DN among type 2 diabetic patients.
Endothelial nitric oxide synthase (eNOS) deficiency may contribute to the pathogenesis of diabetic nephropathy in both experimental models and humans, but the underlying mechanism is not fully understood.
We administered nicorandil to a model of advanced diabetic nephropathy (the streptozotocin-induced diabetes in mice lacking endothelial nitric oxide synthase, eNOSKO); controls included diabetic eNOS KO mice without nicorandil and nondiabetic eNOS KO mice treated with either nicorandil or vehicle.Mice were treated for 8 wk.
The evidence accumulated suggested that 4b/a and G894T polymorphisms in the eNOS gene were associated with susceptibility to DN in Asian populations, but not in Caucasian populations.
However, larger future prospective studies are required to confirm the role of eNOS gene polymorphism in the progression of diabetic nephropathy to ESRD.
Two murine models exploiting endothelial nitric oxide synthase (eNOS) deficiency as a major susceptibility factor for development of diabetic nephropathy are among the very few options for studying features of advanced diabetic nephropathy.
In summary, our meta-analysis of the effect of NOS3 gene polymorphisms on the risk of DN supports the involvement of the NOS3 gene in the pathogenesis of DN.
Our conclusion is that the NOS3-gene may be involved in the development of diabetic nephropathy in patients with type 1 diabetes and can be predictive of CVD during follow-up.