Cellular and Vascular Biology, Paris7/Denis Diderot University, INTS, Paris, France.
Clin Hemorheol Microcirc. 2010;45(2-4):143-53. doi: 10.3233/CH-2010-1292.
Elevated glucose concentration increases oxidation and Advanced Glycation End product (AGE) formation. The binding of circulatory AGEs or AGEs included in erythrocyte membrane to the receptor for AGEs (RAGE) generates in endothelial cells an oxidative stress and enhances the expression of inflammatory molecules. Engagement of RAGE by AGEs and subsequent signaling plays an important role in the development of diabetic complications. Soluble RAGE isoforms (sRAGE) neutralize the ligand-mediated damage by acting as a decoy. If the expression of RAGE is upregulated during the pathogenesis of inflammatory diseases, sRAGE mostly found decreased when complications ensue. By modulating RAGE isoform expression, it could be possible to reduce the incidence of complications. This review focused on the capability of Angiotensin Receptor Blockers (ARBs), which are used to treat patients with hypertension and/or diabetes, to modulate RAGE isoform expression because some data reported the interference with RAGE downstream. In this regard, three ARBs - irbesartan, telmisartan, candesartan cilexetil - were tested and provided evidence for their ability to inhibit in human endothelial cells the expression of membrane-bound and soluble RAGE isoforms induced by the inflammatory factor Tumor Necrosis Factor-alpha (TNF-alpha), demonstrating the potential benefits of these molecules in RAGE-oriented therapies. Modulating RAGE isoforms expression by correcting endothelial dysfunction is achievable by drugs already used for hypertension or diabetes treatment such as ARBs.
高浓度葡萄糖会增加氧化和晚期糖基化终产物（AGE）的形成。循环 AGE 或包含在红细胞膜中的 AGE 与 AGE 受体（RAGE）结合，在内皮细胞中产生氧化应激，并增强炎症分子的表达。AGE 与 RAGE 的结合及其随后的信号转导在糖尿病并发症的发展中起着重要作用。可溶性 RAGE 同种型（sRAGE）通过充当诱饵来中和配体介导的损伤。如果在炎症性疾病的发病机制中 RAGE 的表达上调，则在并发症发生时通常会发现 sRAGE 减少。通过调节 RAGE 同种型的表达，有可能降低并发症的发生率。这篇综述重点介绍了血管紧张素受体阻滞剂（ARBs）的能力，这些药物用于治疗高血压和/或糖尿病患者，因为一些数据报告了它们对 RAGE 下游的干扰。在这方面，测试了三种 ARB-厄贝沙坦、替米沙坦和坎地沙坦西酯-并提供了它们抑制由炎症因子肿瘤坏死因子-α（TNF-α）诱导的人内皮细胞膜结合和可溶性 RAGE 同种型表达的能力的证据，证明了这些分子在 RAGE 靶向治疗中的潜在益处。通过纠正内皮功能障碍来调节 RAGE 同种型的表达，可以通过已经用于高血压或糖尿病治疗的药物（如 ARBs）来实现。
