RAGE and soluble RAGE: Potential therapeutic targets for cardiovascular diseases
RAGE and soluble RAGE: Potential therapeutic targets for cardiovascular diseases
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DOI：
10.2119/2007-00087.koyama
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发表时间：
2007-11-01
影响因子：
5.7
通讯作者：
Nishizawa, Yoshiki
中科院分区：
文献类型：
--
作者：
Koyama, Hidenori;Yamamoto, Hiroshi;Nishizawa, Yoshiki
晚期糖基化终产物受体（RAGE）被认为与糖尿病微血管并发症有关。RAGE还通过调节动脉粥样硬化、血管生成反应、血管损伤和炎症反应与糖尿病大血管并发症密切相关。RAGE在心血管疾病发病机制中的潜在意义似乎不仅仅局限于非糖尿病，而不仅仅局限于糖尿病。近年来，人们对RAGE的许多截短形式进行了描述，其中c端截短的RAGE可溶形式受到了广泛的关注。可溶性RAGE由几种形式组成，包括内源性分泌型RAGE (esRAGE)，这是RAGE的剪接变体，以及来自细胞表面的脱落型RAGE。这些异质形式的可溶性RAGE携带所有的细胞外结构域，但缺乏跨膜和胞质内结构域，结合包括AGEs在内的配体，可以在体外和体内拮抗RAGE信号。ELISA系统已被开发用于测定血浆esRAGE和总可溶性RAGE，并且可溶性RAGE的病理生理作用已开始在临床上被揭示。在这篇综述中，我们总结了RAGE和可溶性RAGE在心血管疾病中的病理生理作用的最新发现，并讨论了它们作为该疾病的治疗靶点和生物标志物的潜在用途。
Receptor for advanced glycation end-products (RAGE) is known to be involved in microvascular complications in diabetes. RAGE is also profoundly associated with macrovascular complications in diabetes through regulation of atherogenesis, angiogenic response, vascular injury, and inflammatory response. The potential significance of RAGE in the pathogenesis of cardiovascular disease appears not to be confined solely to nondiabetic rather than diabetic conditions. Numerous truncated forms of RAGE have recently been described, and the C-terminally truncated soluble form of RAGE has received much attention. Soluble RAGE consists of several forms, including endogenous secretory RAGE (esRAGE), which is a spliced variant of RAGE, and a shedded form derived from cell-surface RAGE. These heterogeneous forms of soluble RAGE, which carry all of the extracellular domains but are devoid of the transmembrane and intracytoplasmic domains, bind ligands including AGEs and can antagonize RAGE signaling in vitro and in vivo. ELISA systems have been developed to measure plasma esRAGE and total soluble RAGE, and the pathophysiological roles of soluble RAGE have begun to be unveiled clinically. In this review, we summarize recent findings regarding pathophysiological roles in cardiovascular disease of RAGE and soluble RAGE and discuss their potential usefulness as therapeutic targets and biomarkers for the disease.