Basta Giuseppina
CNR, Institute of Clinical Physiology, San Cataldo Research Area, Via Moruzzi 1, 56124 Pisa, Italy.
Atherosclerosis. 2008 Jan;196(1):9-21. doi: 10.1016/j.atherosclerosis.2007.07.025. Epub 2007 Sep 10.
The receptor for advanced glycation endproducts (RAGE) is a member of the immunoglobulin superfamily of cell-surface molecules with a diverse repertoire of ligands. In the atherosclerotic milieu, three classes of RAGE ligands, i.e., products of non-enzymatic glycoxidation, S100 proteins and amphoterin, appear to drive receptor-mediated cellular activation and potentially, acceleration of vascular disease. The interaction of RAGE-ligands effectively modulates several steps of atherogenesis, triggering an inflammatory-proliferative process and furthermore, critically contributing to propagation of vascular perturbation, mainly in diabetes. RAGE has a circulating truncated variant isoform, soluble RAGE (sRAGE), corresponding to its extracellular domain only. By competing with cell-surface RAGE for ligand binding, sRAGE may contribute to the removal/neutralization of circulating ligands thus functioning as a decoy. The critical role of RAGE in the chronic vascular inflammation processes highlights this receptor-ligand axis as a possible and attractive candidate for therapeutic intervention to limit vascular damage and its associated clinical disorders.
晚期糖基化终末产物受体（RAGE）是细胞表面分子免疫球蛋白超家族的成员，其配体种类繁多。在动脉粥样硬化环境中，三类RAGE配体，即非酶糖氧化产物、S100蛋白和两性蛋白，似乎驱动受体介导的细胞活化，并可能加速血管疾病。RAGE配体的相互作用有效地调节动脉粥样硬化形成的几个步骤，引发炎症增殖过程，进而对血管紊乱的传播起关键作用，主要发生在糖尿病中。RAGE有一个循环截短的变异体亚型，可溶性RAGE（sRAGE），仅对应其细胞外结构域。通过与细胞表面RAGE竞争配体结合，sRAGE可能有助于清除/中和循环配体，从而起到诱饵作用。RAGE在慢性血管炎症过程中的关键作用突出了这个受体-配体轴作为限制血管损伤及其相关临床疾病的治疗干预的一个可能且有吸引力的候选靶点。
