Nakamura Kazuo, Yamagishi Sho-ichi, Adachi Hisashi, Matsui Takanori, Kurita-Nakamura Yayoi, Takeuchi Masayoshi, Inoue Hiroyoshi, Imaizumi Tsutomu
Nakamura Clinic, Kita-Kyushu, Kurume University School of Medicine, Kurume, Japan.
Microvasc Res. 2008 May;76(1):52-6. doi: 10.1016/j.mvr.2007.09.004. Epub 2007 Oct 5.
We have recently found that soluble form of receptor for advanced glycation end products (sRAGE) levels are positively associated with inflammatory biomarkers and the presence of coronary artery disease (CAD) in type 2 diabetic patients. Since advanced glycation end products (AGEs) up-regulate RAGE expression and endogenous sRAGE could be generated from the cleavage of cell surface RAGE, it is conceivable that sRAGE is positively associated with circulating AGEs levels in diabetes. In this study, we examined whether sRAGE were correlated to circulating levels of AGEs and soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in patients with type 2 diabetes. Eighty-two Japanese type 2 diabetic patients underwent a complete history and physical examination, determination of blood chemistries, sRAGE, AGEs, sVCAM-1 and sICAM-1. Multiple regression analysis revealed that serum levels of AGEs and sVCAM-1 were independently correlated with sRAGE. This study demonstrated that serum levels of sRAGE were positively associated with circulating AGEs and sVCAM-1 levels in type 2 diabetic patients. Our present observations suggest sRAGE level may be elevated in response to circulating AGEs, thus being a novel marker of vascular injury in patients with type 2 diabetes.
我们最近发现,晚期糖基化终末产物受体的可溶性形式(sRAGE)水平与2型糖尿病患者的炎症生物标志物及冠状动脉疾病(CAD)的存在呈正相关。由于晚期糖基化终末产物(AGEs)上调RAGE表达,且内源性sRAGE可由细胞表面RAGE的裂解产生,因此可以推测sRAGE与糖尿病患者循环中的AGEs水平呈正相关。在本研究中,我们检测了2型糖尿病患者中sRAGE是否与循环中的AGEs水平以及血管细胞黏附分子-1的可溶性形式(sVCAM-1)和细胞间黏附分子-1的可溶性形式(sICAM-1)相关。82名日本2型糖尿病患者接受了完整的病史和体格检查、血液化学指标测定、sRAGE、AGEs、sVCAM-1和sICAM-1检测。多元回归分析显示,AGEs和sVCAM-1的血清水平与sRAGE独立相关。本研究表明,2型糖尿病患者中sRAGE的血清水平与循环中的AGEs和sVCAM-1水平呈正相关。我们目前的观察结果表明,sRAGE水平可能因循环中的AGEs而升高,因此是2型糖尿病患者血管损伤的一个新标志物。