Koyama Hidenori, Shoji Takuhito, Yokoyama Hisayo, Motoyama Kohka, Mori Katsuhito, Fukumoto Shinya, Emoto Masanori, Shoji Tetsuo, Tamei Hironori, Matsuki Hirokazu, Sakurai Shigeru, Yamamoto Yasuhiko, Yonekura Hideto, Watanabe Takuo, Yamamoto Hiroshi, Nishizawa Yoshiki
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2587-93. doi: 10.1161/01.ATV.0000190660.32863.cd. Epub 2005 Oct 13.
Advanced glycation endproducts, AGEs, and its specific receptor, RAGE, are involved in diabetic vascular complications. Endogenous secretory RAGE, esRAGE, has been identified as an alternatively spliced form of RAGE, and shown to act as a decoy receptor for AGE. Here, we measured plasma esRAGE level with a recently developed enzyme-linked immunosorbent assay (ELISA) and examined its association with atherosclerosis in age- and gender-matched 203 type 2 diabetic and 134 nondiabetic subjects.
Plasma esRAGE was inversely associated with carotid or femoral atherosclerosis, as quantitatively measured as intimal-medial thickness (IMT) by arterial ultrasound. Stepwise regression analyses revealed that plasma esRAGE was the third strongest and independent factor associated with carotid IMT, following age and systolic blood pressure. Plasma esRAGE was significantly lower in diabetic patients (0.176+/-0.092 ng/mL) than nondiabetic controls (0.253+/-0.111). Of note, in all, diabetic or nondiabetic group, plasma esRAGE was significantly and inversely correlated with components of the metabolic syndrome including body mass index, blood pressure, triglyceride, HbA1c, or an insulin resistance index. Stepwise regression analyses showed that body mass index or insulin resistance index was the major factor determining plasma esRAGE in all, nondiabetic or diabetic population.
esRAGE is a novel and potential protective factor for the metabolic syndrome and atherosclerosis.
晚期糖基化终产物（AGEs）及其特异性受体（RAGE）与糖尿病血管并发症有关。内源性分泌型RAGE（esRAGE）已被鉴定为RAGE的一种选择性剪接形式，并被证明可作为AGE的诱饵受体。在此，我们使用最近开发的酶联免疫吸附测定（ELISA）法测量了血浆esRAGE水平，并在年龄和性别匹配的203例2型糖尿病患者和134例非糖尿病患者中研究了其与动脉粥样硬化的关系。
通过动脉超声定量测量内膜中层厚度（IMT），结果显示血浆esRAGE与颈动脉或股动脉粥样硬化呈负相关。逐步回归分析显示，血浆esRAGE是继年龄和收缩压之后与颈动脉IMT相关的第三大且独立的因素。糖尿病患者的血浆esRAGE（0.176±0.092 ng/mL）显著低于非糖尿病对照组（0.253±0.111）。值得注意的是，在所有糖尿病或非糖尿病组中，血浆esRAGE与代谢综合征的各项指标包括体重指数、血压、甘油三酯、糖化血红蛋白或胰岛素抵抗指数均呈显著负相关。逐步回归分析表明，体重指数或胰岛素抵抗指数是决定所有非糖尿病或糖尿病人群血浆esRAGE水平的主要因素。
esRAGE是代谢综合征和动脉粥样硬化的一种新型潜在保护因子。
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