Soluble RAGE and atherosclerosis in youth with type 1 diabetes: a 5-year follow-up study.
Soluble RAGE and atherosclerosis in youth with type 1 diabetes: a 5-year follow-up study.
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DOI：
10.1186/s12933-015-0292-2
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发表时间：
2015-09-25
影响因子：
9.3
通讯作者：
Dahl-Jørgensen K
中科院分区：
文献类型：
--
作者：
Heier M;Margeirsdottir HD;Gaarder M;Stensæth KH;Brunborg C;Torjesen PA;Seljeflot I;Hanssen KF;Dahl-Jørgensen K
晚期糖基化终末产物（AGEs）通过与晚期糖基化终末产物受体β 1的结合在糖尿病晚期并发症和动脉粥样硬化的发展中发挥作用。受体结合导致血管内皮的活化和血管壁中的炎症增加。该受体的可溶性变体，内源性分泌型β-内酰胺酶（esophagus）和β-内酰胺酶的裂解细胞表面部分，它们一起构成可溶性β-内酰胺酶（sophagus），被认为具有作为β-内酰胺酶诱饵的保护作用。我们的目的是测试高水平的可溶性β-淀粉样蛋白变体是否可以预防动脉粥样硬化的发展。对动脉粥样硬化和儿童糖尿病前瞻性研究的参与者在基线（8 - 18岁）和5年后的随访时进行了检查。通过免疫测定法测定了299例1型糖尿病患者和112例健康对照者的基线和241例患者和128例对照者的sCRP和esCRP。用免疫分析法测定AGEs甲基甘氨酸衍生的氢咪唑酮-1（MG-H1）和羧甲基赖氨酸（CML）。评估的动脉粥样硬化的替代标志物是颈动脉内膜中层厚度（cIMT）、C反应蛋白（CRP）和杨氏模量，分别是动脉壁厚度、炎症和动脉硬度的测量值。在糖尿病患者和对照组中，基线和随访时的sodium和esodium水平均密切相关。随着年龄的增长，这两个变量的平均值下降，独立于性别，糖尿病或青春期阶段。在糖尿病组中，多元回归分析显示可溶性β-淀粉样蛋白的两种变体与cIMT呈正相关。与杨氏模量无显著相关性，但基线时的sCRP与随访时的CRP呈负相关。与对照组相比，糖尿病患者中AGEs和可溶性糖基化酶变体之间的比率增加。结果显示，在基线时高水平的sodium对5年后的炎症可能具有保护作用，但在该T1D青少年和年轻成人队列中，对动脉硬度或壁厚度没有保护作用。
Advanced glycation end products (AGEs) play a role in the development of late complications and atherosclerosis in diabetes by engaging the receptor for advanced glycation end products, RAGE. Receptor binding leads to activation of the vascular endothelium and increased inflammation in the vessel wall. The soluble variants of the receptor, endogenous secretory RAGE (esRAGE) and the cleaved cell-surface part of RAGE, which together comprise soluble RAGE (sRAGE), are suggested to have a protective effect acting as decoys for RAGE. We aimed to test whether high levels of soluble variants of RAGE could be protective against atherosclerosis development. Participants in the prospective atherosclerosis and childhood diabetes study were examined at baseline (aged 8–18) and at follow-up after 5 years. Both sRAGE and esRAGE were measured by immunoassay in 299 patients with type 1 diabetes and 112 healthy controls at baseline and 241 patients and 128 controls at follow-up. The AGEs methylglyoxal-derived hydroimidazolone-1 (MG-H1) and carboxymethyllysine (CML) were measured by immunoassay. The surrogate markers of atherosclerosis assessed were carotid intima-media thickness (cIMT), C-reactive protein (CRP) and Young’s modulus, measures of arterial wall thickness, inflammation and arterial stiffness, respectively. Levels of sRAGE and esRAGE correlated strongly both at baseline and at follow-up in both diabetes patients and controls. With increasing age, mean values of both variants declined, independent of gender, diabetes or pubertal stage. In the diabetes group, multiple regression analysis showed a positive association between both variants of soluble RAGE and cIMT. There was no significant relationship with Young’s modulus, but a negative association between sRAGE at baseline and CRP at follow-up. The ratios between the AGEs and the variants of soluble RAGE were increased in diabetes patients compared to controls. The results show a possible protective effect of high levels of sRAGE at baseline against inflammation 5 years later, but not on arterial stiffness or wall thickness, in this cohort of adolescents and young adults with T1D.