The receptor for advanced glycation end products (RAGE) and DIAPH1: unique mechanisms and healing the wounded vascular system.
The receptor for advanced glycation end products (RAGE) and DIAPH1: unique mechanisms and healing the wounded vascular system.
复制标题
晚期糖基化终末产物 (RAGE) 和 DIAPH1 的受体：独特的机制和治愈受伤的血管系统。
DOI：
10.1080/14789450.2018.1536551
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发表时间：
2019
影响因子：
3.4
通讯作者：
Schmidt,AnnMarie
中科院分区：
文献类型：
--
作者：
Ramasamy,Ravichandran;Friedman,RichardA;Shekhtman,Alexander;Schmidt,AnnMarie
心血管疾病是发病率和死亡率的主要原因，特别是在糖尿病患者中。最近的研究强调，针对炎症的治疗，如白细胞介素-1β拮抗剂，对有心肌梗死病史且具有高敏感性c反应蛋白> 2 mg/L水平的患者有显著的心血管益处。这种治疗减少了非致死性心肌梗死、中风或心血管原因的死亡，其方式与血脂无关。然而，先天免疫系统的分子可能是一把双刃剑。戈麦斯和他的同事报告说，在18到26周的饮食中，给缺乏Apoe的西方饮食喂养的小鼠注射抗il - 1抗体是有害的；平滑肌细胞（SMC）和病变胶原含量被抗体抑制，并伴有病变巨噬细胞[2]的增加。这些考虑强调了针对先天免疫功能分子可能产生的有害影响，并确认对于每种特定分子，了解其时间和细胞类型特异性机制在不同的炎症血管环境中可能不同是至关重要的。晚期糖基化终产物受体（RAGE）是免疫球蛋白超家族的一员。尽管RAGE的发现是由于其能够转导晚期糖基化终产物（AGEs）的细胞内信号，AGEs在高血糖、衰老和肥胖中积累，但其结合非age配体（如S100/calgranulins和高迁移率组Box 1 (HMGB1)）的能力与炎症有关。死亡和垂死细胞释放RAGE配体的观察表明，一旦启动，RAGE依赖的炎症过程可能难以平息，因为在受伤的脉管系统中，配体产生的刺激、它们的来源和细胞释放的条件可能各不相同，但都是持续的。最近，关于RAGE在受血管疾病困扰的不同储存库中令人惊讶的多样性作用的细微差别已经出现。在这篇社论中，我们阐明了中心假设，尽管从RAGE到血管损伤的道路可能不同，但结果会造成损伤和预先修复。精确定位RAGE生物学中的调节开关可能会释放出新的血管特异性策略，以治愈受伤的心脏和由其支流喂养的组织。
Cardiovascular disease represents a leading cause of morbidity and mortality, particularly in subjects with diabetes. Recent studies have highlighted that therapies targeting inflammation, such as antagonism of Interleukin-1β, exert significant cardiovascular benefit in patients with a history of myocardial infarction and possessing a level of high sensitivity C-reactive protein> 2 mg/L. This treatment reduced nonfatal myocardial infarction, stroke or death from cardiovascular cause, in a manner independent of lipid profile [1]. Yet, molecules of the innate immune system may bear double-edged swords. Gomez and colleagues reported that administration of an anti-IL1 antibody to Western diet-fed mice devoid of Apoe between 18 and 26 weeks of diet was deleterious; smooth muscle cell (SMC) and lesional collagen content were suppressed by antibody treatment and were accompanied by increased lesional macrophages [2]. Such considerations underscore the possible detrimental effects of targeting innate immune function molecules and affirm that for each specific molecule, understanding that its timeand cell type-specific mechanisms may differ in distinct inflamed vascular milieus, is critical. The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily. Although RAGE was discovered on account of its ability to transduce the intracellular signals of advanced glycation end products (AGEs), which accumulate in hyperglycemia, aging, and obesity, its ability to bind non-AGE ligands, such as S100/calgranulins and high mobility group Box 1 (HMGB1), implicated RAGE in inflammation. The observation that dead and dying cells release RAGE ligands suggests that once set in motion, RAGE-dependent inflammatory processes may be challenging to quell, as both the instigating stimuli to ligand production, and their sources and conditions of cellular release may be varied, but sustained, in the wounded vasculature [3]. Recently, nuances have emerged regarding a surprising diversity of RAGE actions in distinct depots beset by vascular disease. In this Editorial, we articulate the central hypothesis that although the roads leading from RAGE to vascular wounds may differ, the outcome yields damage and forestalled repair. Pinpointing the regulatory switches in RAGE biology may unleash novel vascular-specific strategies to heal the wounded heart and the tissues fed by its tributaries.