Olmesartan blocks advanced glycation end products (AGEs)-induced angiogenesis in vitro by suppressing receptor for AGES (RAGE) expression
Olmesartan blocks advanced glycation end products (AGEs)-induced angiogenesis in vitro by suppressing receptor for AGES (RAGE) expression
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DOI：
10.1016/j.mvr.2007.05.001
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Imaizumi, Tsutomu
中科院分区：
文献类型：
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作者：
Yamagishi, Sho-ichi;Matsui, Takanori;Imaizumi, Tsutomu
我们已经证明晚期糖基化终产物(AGEs)-其受体(RAGE)的相互作用通过自分泌血管内皮生长因子(VEGF)来诱导血管生成，从而提示AGEs-RAGE系统积极参与增殖性糖尿病视网膜病变(PDR)。由于AGEs-RAGE和肾素-血管紧张素系统之间的相互作用在PDR的发病机制中也被提出，我们在这里研究了血管紧张素II I型受体阻滞剂奥美沙坦是否通过抑制核因子-kappaB介导的RAGE的表达而在体外抑制AGEs诱导的血管生成。奥美沙坦显著抑制AGEs诱导的微血管内皮细胞(ECs)核因子-kappaB启动子活性和RAGE基因表达。进一步研究发现，奥美沙坦可阻断AGEs诱导的内皮细胞血管内皮生长因子mRNA水平的上调和DNA合成的增加。这些结果首次证明奥美沙坦通过抑制血管内皮细胞RAGE的表达来抑制AGEs的血管生成信号。我们目前的研究表明，奥美沙坦阻断肾素-血管紧张素系统可能通过下调RAGE来减轻AGEs的有害影响，从而起到保护PDR的作用。(C)2007 Elsevier Inc.保留所有权利。
We have previously shown that advanced glycation end products (AGEs)-their receptor (RAGE) interaction elicits angiogenesis through autocrine production of vascular endothelial growth factor (VEGF), thus suggesting the active involvement of the AGEs-RAGE system in proliferative diabetic retinopathy (PDR). Since the crosstalk between the AGEs-RAGE and the renin-angiotensin system has also been proposed in the pathogenesis of PDR, we investigated here whether olmesartan, an angiotensin II type I receptor blocker, inhibited the AGEs-elicited angiogenesis in vitro by suppressing the NF-kappa B-mediated RAGE expression. Olmesartan significantly inhibited the AGEs-induced NF-kappa B promoter activity and RAGE gene expression in cultured microvascular endothelial cells (ECs). Further, olmesartan was found to block the AGEs-induced up-regulation of VEGF mRNA levels and consequent increase in DNA synthesis in ECs. These results demonstrated for the first time that olmesartan inhibited the AGEs signaling to angiogenesis by suppressing RAGE expression in ECs. Our present study suggests that blockade of the renin-angiotensin system by olmesartan may play a protective role against PDR by attenuating the deleterious effects of AGEs via down-regulation of RAGE. (c) 2007 Elsevier Inc. All rights reserved.