"Ohomem nunca pode parar de sonhar. O sonho e o alimento da alma, como a comida eo alimento do corpo."Sonho que um dia todos os especialistas em Nutricao tenham lido sobre AGEs - Produtos de Glicacao Avancada e suas complicacoes para a saude humana. Advanced glycation end products accelerate rat vascular calcification through RAGE/oxidative stressQin Wei1, Xiaomei Ren2, Yibo Jiang3, Hong Jin1, Naifeng Liu1* and Jie Li2*Corresponding author: Naifeng Liu liunf@seu.edu.cnAuthor Affiliations1Department & Institute of Cardiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P. R. China2Department of Geratology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P. R. China3Department of Cardiology, Taixing Hospital affiliated with Yangzhou University, Jiangsu 225400, P. R. ChinaFor all author emails, please log on.BMC Cardiovascular Disorders 2013, 13:13 doi:10.1186/1471-2261-13-13The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2261/13/13Received:31 July 2012Accepted:19 February 2013Published:5 March 2013 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.AbstractBackgroundArterial media calcification (AMC) is highly prevalent and is a major cause of morbidity, mortality, stroke and amputation in patients with diabetes mellitus (DM). Previous research suggests that advanced glycation end products (AGEs) are responsible for vascular calcification in diabetic patients. The potential link between oxidative stress and AGEs-induced vascular calcification, however, has not been examined.MethodsMale Wistar rats received a high fat diet for 8 weeks followed by a single dose of streptozotocin to induce DM (DM). Calcification was induced with Vitamin D3 and nicotine (VDN). We started VDN treatment at 1 week after the initial streptozotocin injection (DM+VDN). Age-matched rats were used as controls (CON). Metabolic parameters, aortic calcium content, alkaline phosphatase (ALP) protein, malondialdehyde (MDA) content, Cu/Zn superoxide dismutase (SOD) activity, aorta receptor for advanced glycation end products (RAGE) and aorta AGEs levels were measured. In vitro, vascular smooth muscle cells (VSMCs) were cultured with AGEs in DMEM containing 10 mmolL-1 -glycerophosphate (-GP). Calcium content and ALP activity were used to identify osteoblastic differentiation and mineralization. Western blots were used to examine protein expression of Cu/Zn SOD, NADPH oxidase Nox1 and RAGE. In addition, the intracellular reactive oxygen species (ROS) generation was evaluated using fluorescent techniques with dihydroethidine (DHE) method.ResultsThe DM+VDN group showed a significant increase in aortic calcium content, levels of aorta AGEs, MDA content, ALP protein levels and RAGE expression, although Cu/Zn SOD activity decreased significantly. In vitro, enhanced Nox1, RAGE expression as well as the production of intracellular superoxide anions, and reduced expression of Cu/Zn SOD induced by AGEs were attenuated by the anti-RAGE antibody or a ROS inhibitor. Furthermore, the AGEs-stimulated ROS increase was also significantly inhibited by a SOD mimetic. Increased ALP activity and calcium deposition were also inhibited markedly by the ROS inhibitor and the anti-RAGE antibody.ConclusionsThese results suggest that AGEs enhance vascular calcification partly through a RAGE/oxidative stress pathway.Keywords: Diabetes mellitus; Advanced glycation end products; Vascular smooth muscle cells; Calcification; Oxidative stresshttp://www.biomedcentral.com/1471-2261/13/13Produtos de glicacao avancada (AGEs) sao compostos