Endogenous Secretory RAGE as a Novel Biomarker for Metabolic Syndrome and Cardiovascular Diseases
Endogenous Secretory RAGE as a Novel Biomarker for Metabolic Syndrome and Cardiovascular Diseases
复制标题
DOI：
10.4137/117727190700200021
复制
发表时间：
2007-01
影响因子：
3.8
通讯作者：
H. Koyama;Hiroshi Yamamoto;Y. Nishizawà
中科院分区：
文献类型：
--
作者：
H. Koyama;Hiroshi Yamamoto;Y. Nishizawà
晚期糖基化终产物受体（Receptor for Advanced Glycation End Products，RECEPTOR）参与糖尿病微血管和大血管并发症的发生。在最近描述的许多截短形式的cDNAs中，cDNAs的C-末端截短形式受到了很多关注。携带所有胞外结构域但缺乏跨膜和胞质内结构域的这种形式的β-淀粉样蛋白从细胞外释放，结合包括AGE在内的配体，并且能够中和培养物中内皮细胞上的β-淀粉样蛋白信号传导。这种形式的β-淀粉样蛋白是作为剪接变体产生的，并被命名为内源性分泌型β-淀粉样蛋白（esophageal β-淀粉样蛋白）。腺病毒过表达Esplatin逆转糖尿病血管功能障碍的损害，表明Esplatin可能是体内Esplatin信号传导的重要抑制剂，并可能用于预防糖尿病血管并发症。近年来发展了一种测定血浆雌二醇的ELISA系统，雌二醇的病理生理作用已开始在临床上得到揭示。血浆雌二醇水平在患有几种代谢疾病的患者中降低，包括1型和2型糖尿病、代谢综合征和高血压。在横断面分析中，血浆雌二醇水平与颈动脉或股动脉粥样硬化呈负相关。在终末期肾病患者的观察性队列中，血浆雌二醇水平较低的受试者心血管死亡的累积发生率显著较高。这些结果表明，血浆雌二醇可能作为一种保护因素，对代谢综合征和心血管疾病的发生和一种新的生物标志物。
Receptor for advanced glycation end-products (RAGE) is known to be involved in both micro- and macrovascular complications in diabetes. Among numerous truncated forms of RAGE recently described, the C-terminally truncated form of RAGE has received much attention. This form of RAGE, carrying all of the extracellular domains but devoid of the trans-membrane and intracytoplasmic domains, is released outside from cells, binds ligands including AGEs, and is capable of neutralizing RAGE signaling on endothelial cells in culture. This form of RAGE is generated as a splice variant and is named endogenous secretory RAGE (esRAGE). Adenoviral overexpression of esRAGE reverses diabetic impairment of vascular dysfunction, suggesting that esRAGE may be an important inhibitor of RAGE signaling in vivo and potentially be useful for prevention of diabetic vascular complications. An ELISA system to measure plasma esRAGE was recently developed, and the pathophysiological roles of esRAGE have begun to be unveiled clinically. Plasma esRAGE levels are decreased in patients with several metabolic diseases including type 1 and type 2 diabetes, metabolic syndrome and hypertension. In cross-sectional analysis, plasma esRAGE levels are inversely correlated with carotid or femoral atherosclerosis. In an observational cohort of patients with end-stage renal disease, cumulative incidence of cardiovascular death was significantly higher in subjects with lower plasma esRAGE levels. These findings suggest that plasma esRAGE may act as a protective factor against and a novel biomarker for the occurrence of metabolic syndrome and cardiovascular diseases.