Division of Cardiology, Yonsei University College of Medicine, Seoul, South Korea.
Front Biosci (Landmark Ed). 2011 Jan 1;16(2):486-97. doi: 10.2741/3700.
RAGE is pattern recognizing receptors for diverse endogenous ligands. RAGE activation by RAGE ligands is known to be associated with reactive oxygen species generation, activation of NF kappa B, as well as recruitment of proinflammatory cells. Activated endothelial cells, vascular smooth muscle cells in atherosclerotic plaques and activated inflammatory cells all have increased expression of RAGE, which with its interaction with RAGE ligands increases the secretion of proinflammatory cytokines and cell adhesion molecules. Furthermore, RAGE may have a significant role in leukocyte recruitment into the intima of the atherosclerosis. Initial insults resulting in endothelial dysfunction will result in leukocyte infiltration, oxidative stress and vascular inflammation that is amplified by RAGE activation. RAGE and its interaction with RAGE ligands may be important for initializing and maintaining the pathological processes that result in various entities of cardiovascular disease. Soluble RAGE competitively inhibits the binding of RAGE ligands to RAGE and attenuates the development of atherosclerosis in vivo. Thus RAGE may be a promising target for treatment of cardiovascular disease in the future.
RAGE 是识别多种内源性配体的模式识别受体。已知 RAGE 配体激活 RAGE 与活性氧物种的生成、NF-κB 的激活以及促炎细胞的募集有关。在动脉粥样硬化斑块中，激活的内皮细胞、血管平滑肌细胞和激活的炎症细胞均表现出 RAGE 的表达增加，RAGE 与其配体的相互作用增加了促炎细胞因子和细胞黏附分子的分泌。此外，RAGE 可能在白细胞募集到动脉粥样硬化内膜中发挥重要作用。最初的损伤导致内皮功能障碍，从而导致白细胞浸润、氧化应激和血管炎症，这些炎症反应会被 RAGE 的激活放大。RAGE 及其与 RAGE 配体的相互作用可能对启动和维持导致各种心血管疾病实体的病理过程很重要。可溶性 RAGE 竞争性抑制 RAGE 配体与 RAGE 的结合，并减弱体内动脉粥样硬化的发展。因此，RAGE 可能是未来治疗心血管疾病的一个有前途的靶点。
