Ospital, Southeast University, Nanjing, Jiangsu 210009, P. R. China Full list of author information is available at the end of the articlemorbidity, mortality, stroke and amputation rates [1-4]. Over recent years, several studies have revealed that vascular calcification is an actively regulated process that is similar to osteogenesis. Advanced glycation end products (AGEs) derived from reducing sugars reaction non-enzymatically with amino groups of protein play an important role in the pathogenesis of numerous diseases, including diabetic complications, atherosclerosis and aging. AGEs are formed at an accelerated rate under diabetic states and during renal failure [5]. Recently, considerable evidences have suggested?2013 Wei et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Wei et al. BMC Cardiovascular Disorders 2013, 13:13 http://www.biomedcentral.com/1471-2261/13/Page 2 ofthat AGEs might contribute to vascular calcification. AGEs have the ability to accelerate calcification in microvascular pericytes, which could contribute to the development of vascular calcification [6]. A study by Taki K et al. showed a positive correlation between serum AGEs levels and the severity of coronary artery calcification in hemodialysis patients [7]. Alexi Baidoshvilia et al. found that in DM patients, N (epsilon)-(carboxymethyl)lysine (CML), a main antigenic structure of non-cross linking AGEs, accumulated on calcification sites in degenerated aortic valves and in internal thoracic arteries [8]. Indeed, GGTI298MedChemExpress GGTI298 Previous data showed that AGEs enhanced calcification in vascular smooth muscle cells (VSMCs) through the receptor for AGEs (RAGE) pathway [9,10]. Therefore, these results suggest that AGEs are responsible for vascular calcification in diabetic patients. Vascular reactive oxygen species (ROS) contribute to vascular functional and structural alterations. At the cellular levels, ROS can result in the reduction of proliferation, apoptosis, cell cycle arrest, and modulation of differentiation [11-13]. Previous study suggested that hydrogen peroxide or xanthine/xanthine oxidase increased intracellular oxidative stress and enhanced osteoblastic differentiation of vascular cells, as demonstrated by their analysis of alkaline phosphatase (ALP) activity and mineralization [14]. Indeed, the engagement of RAGE with AGEs can induce oxidative stress in VSMCs, thereby playing an important role in the development and progression of many diseases [15]. The potential link between oxidative stress and AGEs-induced vascular calcification, however, has not been examined. Given these findings, we hypothesized that AGEs accelerated vascular calcification through the RAGE/oxidative stress pathway in the present study.standard chow for 1 week after the start of the STZ administration. A portion of the diabetic rats were PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27663262 then switched to treatment with a vehicle buffer (0.1 mol -1 sodium citrate buffer, pH 4.5) and a standard chow diet (60 carbohydrates, 22 protein, 10 fat, 8 fiber and other ingredients) (n = 10). For the second group (the DM +VDN group), half of the diabetic rats were treated with a single dose of vitamin D3 (300 000 U/kg, intramuscularly, Sigma) and nicotine (25 mg g-1, 5 ml g-1, PO, Sigma) to induce.