Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, Unity Health Toronto, University of Toronto, Toronto, ON M5B 1T8, Canada.
Department of Internal Medicine, Research Institute and Diabetes Center, Attikon University Hospital, University of Athens Medical School, 124 62 Athens, Greece.
Molecules. 2020 Nov 10;25(22):5235. doi: 10.3390/molecules25225235.
We determined whether plasma concentrations of the receptor for advanced glycation end products (RAGE) and the soluble (s) form of RAGE (sRAGE) in healthy individuals and patients with type 2 diabetes (T2D) modulate vascular remodeling. Healthy individuals and patients with T2D were divided into two age groups: young = <35 years old or middle-aged (36-64 years old) and stratified based on normal glucose tolerance (NGT), impaired (IGT), and T2D. Plasma titers of sRAGE, the RAGE ligands, AGEs, S100B, S100A1, S100A6, and the apoptotic marker Fas ligand Fas(L) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic potential of the above RAGE ligands and sRAGE were assessed in cultured adult rat aortic smooth muscle cells (ASMC). In NGT individuals, aging increased the circulating levels of AGEs and S100B and decreased sRAGE, S100A1 and S100A6. Middle-aged patients with T2D presented higher levels of circulating S100B, AGEs and FasL, but lower levels of sRAGE, S100A1 and S100A6 than individuals with NGT or IGT. Treatment of ASMC with either AGEs or S100B at concentrations detected in T2D patients increased markers of inflammation and apoptosis. Responses attenuated by concomitant administration of sRAGE. In middle-aged patients with T2D, lower circulating plasma levels of sRAGE may limit decoy and exogenous trapping of deleterious pro-apoptotic/pro-inflammatory RAGE ligands AGEs and S100B, increasing the risk for diabetic complications.
我们确定了健康个体和 2 型糖尿病（T2D）患者血浆中晚期糖基化终产物受体（RAGE）和可溶性 RAGE（sRAGE）浓度是否调节血管重塑。健康个体和 T2D 患者分为两个年龄组：年轻组（<35 岁）和中年组（36-64 岁），并根据正常葡萄糖耐量（NGT）、糖耐量受损（IGT）和 T2D 进行分层。通过酶联免疫吸附试验（ELISA）测量 sRAGE、RAGE 配体、AGEs、S100B、S100A1、S100A6 和凋亡标记 Fas 配体 Fas（L）的血浆滴度。在培养的成年大鼠主动脉平滑肌细胞（ASMC）中评估上述 RAGE 配体和 sRAGE 的凋亡潜能。在 NGT 个体中，衰老增加了循环 AGEs 和 S100B 的水平，降低了 sRAGE、S100A1 和 S100A6 的水平。中年 T2D 患者的循环 S100B、AGEs 和 FasL 水平较高，而 sRAGE、S100A1 和 S100A6 水平低于 NGT 或 IGT 个体。用 T2D 患者中检测到的浓度的 AGEs 或 S100B 处理 ASMC，增加了炎症和凋亡标志物。同时给予 sRAGE 可减弱反应。在中年 T2D 患者中，较低的循环血浆 sRAGE 水平可能限制有害促凋亡/促炎 RAGE 配体 AGEs 和 S100B 的诱饵和外源性捕获，增加糖尿病并发症的风险。
