eNOS and Diabetic Nephropathy
- *Corresponding Author:
- Nobuyuki Takahashi
Graduate Schools of Pharmaceutical Sciences and Medicine
Tohoku University, 6-3 Aoba Aramaki Aoba-ku Sendai
Fax: +81-22-795- 6839
E-mail: [email protected]
Received Date: December 23, 2011; Accepted Date: February 23, 2012; Published Date: February 25, 2012
Citation: Li F, Takahashi N (2012) eNOS and Diabetic Nephropathy. J Nephrol Therapeutic S2:004 doi:10.4172/2161-0959.S2-004
Copyright: © 2012 Li F, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) and the number of patients with DN has been increasing rapidly. Development of new effective therapeutic strategies of DN is slow at least partly because of a lack of animal models that recapitulate the features of human DN. Human variants of the endothelial nitric oxide synthase gene (eNOS, NOS3 ) that produce reduced amounts of nitric oxide (NO) are positively associated with DN, although proof of causation is lacking. Recently, several investigators have established animal models of advanced DN using mice unable to synthesize eNOS and have demonstrated that eNOS -/- mice with diabetes develop severe nephropathy. It has been also shown that a high fat diet worsens the DN of the diabetic mice lacking eNOS. However, complete absence of eNOS has not been reported in humans, although reduced levels are not infrequent. Accordingly, heterozygous eNOS +/- mice have been made diabetic and they demonstrated that the decrease in eNOS/ NO comparable to that of NOS3 polymorphisms is sufficient to cause exacerbation of DN. Increased expression of tissue factor (TF), initiator of coagulation, plays a significant role in the DN of the eNOS -/- diabetic mice, as well as in diabetic mice having wild type eNOS. Strategies to ameliorate hypercoagulability could be useful for treatment of DN.