Reduction of Rage Expression by Vitamin D in Isolated Diabetic Rat Aortas

High blood glucose level and advanced glycation end-products (AGE) are the major contributors to the development of vascular complications in diabetes mellitus. The receptors for advanced glycation end-products (RAGE) are upregulated in response to high blood glucose level and may play a role in the occurrence of diabetic-related vascular disease. Vitamin D is widely reported as a cardiovascular protective agent. The present study assessed the effects of 1,25-dihydroxycholecalciferol (1,25-VitD(3)) on the endothelial dependent relaxation (EDR) in organ bath studies and on vascular expression of RAGE by immunohistochemistry studies in aortic samples isolated from rats with experimental diabetes (streptozotocin, 50 mg/kg, single dose). Our findings indicate that: i) in diabetic aortas the EDR was significantly impaired (vs. control) together with a high expression of RAGE in the entire structure of the aortic wall and, ii) ex vivo treatment with 1,25-VitD(3)(0.1 mu M) significantly improved the relaxation response and reduced the aortic expression of RAGE in diabetic vascular samples. In conclusion, low amounts of vitamin D exerts beneficial effects on endothelial function in vitro; in particular, we firstly demonstrated the modulation of RAGE expression in the settings of experimental diabetes. Investigations aimed at elucidating the underlying signal transduction pathways are clearly warranted view the potential therapeutic effect.