Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension
Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension
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DOI：
10.1016/j.mvr.2005.10.002
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发表时间：
2005-11-01
影响因子：
3.1
通讯作者：
Imaizumi, T
中科院分区：
文献类型：
--
作者：
Nakamura, K;Yamagishi, S;Imaizumi, T
越来越多的证据表明，晚期糖基化终产物（AGE）-其受体（AGEs）系统在糖尿病血管并发症的发病机制中起着重要作用。肾素-血管紧张素系统（RAS）也参与了糖尿病血管病变的发生和发展。然而，AGE-RACE系统和RAS之间的串扰尚未完全了解。在这项研究中，我们研究了血管紧张素II（Ang II）1型受体系统的作用，在培养的内皮细胞（EC）和原发性高血压患者的血管紧张素II表达。Ang II上调微血管内皮细胞的β-淀粉样蛋白mRNA水平，随后增加内皮细胞培养基中可溶性β-淀粉样蛋白（saponin）的表达，这两种表达均被市售的Ang II 1型受体拮抗剂替米沙坦完全阻断。此外，发现替米沙坦可降低原发性高血压患者的血清胰岛素水平。这些结果表明，sodium从Ang-II暴露的EC的细胞表面释放。我们目前的研究表明AGE-RAS系统和RAS之间存在交叉作用，并提示血清sRAS水平可能反映了内皮细胞的表达。(c)2005年爱思唯尔公司All rights reserved.
There is a growing body of evidence that the advanced glycation end product (AGE)-their receptor (RAGE) system plays a central role in the pathogenesis of diabetic vascular complication. The renin-angiotensin system (RAS) contributes to the development and progression of diabetic angiopathy as well. However, the cross-talk between the AGE-RAGE system and the RAS is not fully understood. In this study, we examined the role of angiotensin II (Ang II) type 1 receptor system for RAGE expression in cultured endothelial cells (ECs) and in patients with essential hypertension. Ang II up-regulated RAGE mRNA levels of microvascular ECs and subsequently increased the soluble form of RAGE (sRAGE) expression in the medium of ECs, both of which were completely blocked by telmisartan, a commercially available Ang II type 1 receptor antagonist. Furthermore, telmisartan was found to decrease serum levels of sRAGE in patients with essential hypertension. These results demonstrate that sRAGE is released from the cell surface of Ang-II-exposed ECs. Our present study indicates that a cross-talk exists between the AGE-RAGE system and the RAS and suggests that serum levels of sRAGE may reflect endothelial RAGE expression. (c) 2005 Elsevier Inc. All rights reserved.