The receptor for advanced glycation end-products has a central role in mediating the effects of advanced glycation end-products on the development of vascular disease in diabetes mellitus.
The receptor for advanced glycation end-products has a central role in mediating the effects of advanced glycation end-products on the development of vascular disease in diabetes mellitus.
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DOI：
10.1093/ndt/11.supp5.13
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
O. Hori;S. Yan;S. Ogawa;K. Kuwabara;M. Matsumoto;D. Stern;A. Schmidt
中科院分区：
文献类型：
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作者：
O. Hori;S. Yan;S. Ogawa;K. Kuwabara;M. Matsumoto;D. Stern;A. Schmidt
暴露于醛糖糖的蛋白质或脂质经历最初和最终不可逆的修饰，导致所谓的晚期糖基化终产物（AGEs）的形成。由于糖尿病的高血糖特征，AGEs被认为在糖尿病的情况下特别重要。我们的工作已经证明，age与血管壁相互作用的主要手段之一是通过与其细胞受体相互作用，即存在于内皮细胞、平滑肌细胞、系膜细胞、单核吞噬细胞和某些神经元表面的晚期糖基化终产物（RAGE）受体。AGEs与RAGE相互作用，导致单核细胞趋化和氧化应激的诱导。age - rage诱导的细胞氧化应激的后果之一是血管细胞粘附分子-1在内皮表面的表达增强，其关键后果是单核吞噬细胞被吸引到血管壁上。在这两种情况下，age的促炎作用可能在RAGE阻断剂的存在下被抑制，使用抗RAGE F(ab')2或可溶性RAGE（分子的细胞外结构域）。这些数据表明，抑制RAGE可能会干扰单核细胞趋化性和对血管壁的吸引，而血管壁是AGEs沉积/形成的地方，这表明这种干预可能会干扰血管疾病发展的关键步骤，尤其是糖尿病患者。
Proteins or lipids exposed to aldose sugars undergo initial and ultimately irreversible modification resulting in the formation of so-called advanced glycation end-products (AGEs). AGEs are postulated to be especially important in the setting of diabetes mellitus due to hyperglycaemia characteristic of this disorder. Our work has demonstrated that one of the principal means by which AGEs interact with the vascular wall is by interaction with their cellular receptor, the receptor for advanced glycation end-products (RAGE), which is present on the surface of endothelial cells, smooth muscle cells, mesangial cells, mononuclear phagocytes and certain neurons. AGEs interact with RAGE, resulting in the induction of monocyte chemotaxis as well as oxidant stress. One of the consequences of AGE-RAGE-induced cellular oxidant stress is the enhanced expression of vascular cell adhesion molecule-1 on the endothelial surface, a critical consequence of which is the attraction of mononuclear phagocytes into the vessel wall. In both cases, the pro-inflammatory effects of AGEs may be inhibited in the presence of RAGE blockade, using either anti-RAGE F(ab')2 or soluble RAGE, the extracellular domain of the molecule. These data suggest that inhibition of RAGE may interfere with monocyte chemotaxis and attraction into the vessel wall where AGEs deposit/form, suggesting the potential of this intervention to interfere with a critical step in the development of vascular disease, especially in patients with diabetes.