Norata Giuseppe Danilo, Garlaschelli Katia, Grigore Liliana, Tibolla Gianpaolo, Raselli Sara, Redaelli Laura, Buccianti Gherardo, Catapano Alberico Luigi
Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.
Nutr Metab Cardiovasc Dis. 2009 Feb;19(2):129-34. doi: 10.1016/j.numecd.2008.03.004. Epub 2008 Jul 2.
Advanced glycation end products, AGEs, and its specific receptor, RAGE, are involved in vascular complications. A role for the soluble form of RAGE (sRAGE), which acts as a decoy for AGE, has been documented in patients with diabetes but no information is available in non-diabetic subjects. The aim of this study was to investigate the association of plasma levels of sRAGE with cardiometabolic risk factors in the general population. In addition we evaluated the relation of the common -374A/T polymorphism of RAGE with plasma levels of sRAGE. One hundred and seventy-six healthy subjects free of diabetes or coronary artery disease untreated for hypertension, dyslipidemia or cardiometabolic related diseases were randomly selected for this study from the general population. Plasma sRAGE were negatively and significantly correlated with BMI, waist/hip circumference ratio and fasting glycemia, while a positive correlation was observed with apolipoprotein A-I. These correlations were observed mainly in women who showed significantly higher sRAGE levels (1744+/-660 pg/mL vs 1414+/-649 pg/mL; P<0.05). In a stepwise regression analysis waist circumference was independently associated with sRAGE and, when waist circumference was excluded, BMI was independently associated with sRAGE. Finally in overweight subjects (BMI>25 kg/m(2)) plasma sRAGE was significantly lower compared to lean subjects (1460+/-640 pg/mL vs 1710+/-693 pg/mL; P<0.05). In healthy subjects plasma levels of sRAGE were negatively correlated with BMI and waist/hip ratio supporting a possible protective role for these proteins before any evidence of diabetic or vascular complications.
晚期糖基化终产物(AGEs)及其特异性受体RAGE参与血管并发症的发生。可溶性RAGE(sRAGE)作为AGE的诱饵发挥作用,这一作用在糖尿病患者中已有记载,但在非糖尿病受试者中尚无相关信息。本研究旨在探讨普通人群中sRAGE血浆水平与心血管代谢危险因素之间的关联。此外,我们评估了RAGE基因常见的-374A/T多态性与sRAGE血浆水平的关系。从普通人群中随机选取176名无糖尿病或冠状动脉疾病、未接受高血压、血脂异常或心血管代谢相关疾病治疗的健康受试者进行本研究。血浆sRAGE与体重指数(BMI)、腰臀比和空腹血糖呈显著负相关,而与载脂蛋白A-I呈正相关。这些相关性主要在女性中观察到,女性的sRAGE水平显著更高(1744±660 pg/mL对1414±649 pg/mL;P<0.05)。在逐步回归分析中,腰围与sRAGE独立相关,排除腰围因素后,BMI与sRAGE独立相关。最后,超重受试者(BMI>25 kg/m²)的血浆sRAGE水平明显低于瘦受试者(1460±640 pg/mL对1710±693 pg/mL;P<0.05)。在健康受试者中,sRAGE血浆水平与BMI和腰臀比呈负相关,这支持了在出现糖尿病或血管并发症迹象之前,这些蛋白可能具有保护作用。