Elevated tissue factor expression contributes to exacerbated diabetic nephropathy in mice lacking eNOS fed a high fat diet.

Journal of Thrombosis and Haemostasis : JTH
F LiNobuyuki Takahashi

Abstract

 Human eNOS (NOS3) polymorphisms that lower its expression are associated with advanced diabetic nephropathy (DN), and the lack of eNOS accelerates DN in diabetic mice. Diabetes is associated with fibrin deposition. Lack of nitric oxide and fatty acids stimulates the NF-kB pathway, which increases tissue factor (TF).  To test the hypothesis that TF contributes to the severity of DN in the diabetic eNOS(-/-) mice fed a high-fat diet (HF).  We made eNOS(-/-) and wild-type mice diabetic with streptozotocin. Half of them were placed on HF.  Blood glucose levels were not affected by either the diet or eNOS genotype. Lack of eNOS in the diabetic mice increased urinary albumin excretion, glomerulosclerosis, interstitial fibrosis, and glomerular basement membrane thickness. HF by itself did not affect DN in the wild-type mice, but significantly enhanced DN in eNOS(-/-) mice. More than half of diabetic eNOS(-/-) mice on HF died prematurely with signs of thrombotic complications. Diabetic kidneys contained fibrin and TF, and their levels were increased by the lack of eNOS and by HF in an additive fashion. The HF diet increased the kidney expression of inflammatory genes. The increase in TF preceded DN, and administration of an anti-mouse...Continue Reading

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Citations

Nov 6, 2014·Journal of Diabetes Research·Takamune Takahashi, Raymond C Harris
Sep 24, 2011·International Journal of Inflammation·Arthur J Chu
Jan 16, 2016·Journal of Diabetes Research·Li Lai, Yohannes T Ghebremariam
Apr 4, 2015·Progress in Lipid Research·Fabien WauquierYohann Wittrant
Jan 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Chih-Hong WangNobuyuki Takahashi
Jun 11, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Yuji OeNobuyuki Takahashi
Mar 13, 2018·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Muxin YuJialan Shi
Nov 22, 2017·Journal of the American Society of Nephrology : JASN·Soo Youn ChoiHyug Moo Kwon
May 20, 2018·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Shuai LiJohn L Hopper
Jan 5, 2019·Clinical Science·Alessandro PiniArianna Carolina Rosa

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