Decreased plasma soluble RAGE in patients with hypercholesterolemia:: Effects of statins
Decreased plasma soluble RAGE in patients with hypercholesterolemia:: Effects of statins
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DOI：
10.1016/j.freeradbiomed.2007.06.017
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发表时间：
2007-11-01
影响因子：
7.4
通讯作者：
Davi, Giovanni
中科院分区：
文献类型：
--
作者：
Santilli, Francesca;Bucciarelli, Loredana;Davi, Giovanni
晚期糖基化终末产物受体（RECEPTOR）在血管病变部位过度表达。一种可溶性的β-淀粉样蛋白异构体（sNAs）通过作为诱饵来中和配体介导的损伤。我们推测，在高胆固醇血症中，配体-β轴的上调可能是氧化应激导致一氧化氮生物合成受损的桥梁。我们测量了60例高胆固醇血症患者和20例对照者的血浆总胆固醇水平、尿8-异前列腺素（PG）FZa排泄量和血浆不对称二甲基精氨酸（ADMA）水平。在20例无血管疾病的高胆固醇血症受试者中分析了两种结构不同的他汀类药物（普伐他汀和阿托伐他汀）对这些参数的影响。高胆固醇血症患者与正常胆固醇血症患者相比，血浆sodium显著降低，ADMA和尿8-iso-PGF（2 α）升高。与无血管疾病的受试者相比，既往心肌梗死患者接受他汀类药物治疗的8-iso-PGF（2 α）较低，sodium较高，ADMA水平不变。在多变量回归分析中，只有8-iso-PGF（2 α）和ADMA预测了severity水平。用他汀类药物治疗8周与尿8-iso-PGF（2 α）显著降低相关，而只有阿托伐他汀使sIgA水平接近正常值，ADMA水平无变化。高胆固醇血症时，氧化应激和内皮功能障碍介导的动脉粥样硬化的发生发展可能与高胆固醇血症有关。(C)2007年爱思唯尔公司All rights reserved.
The receptor for advanced glycation endproducts (RAGE) is overexpressed at sites of vascular pathology. A soluble RAGE isoform (sRAGE) neutralizes the ligand-mediated damage by acting as a decoy. We hypothesized that in hypercholesterolemia up-regulation of the ligand-RAGE axis may bridge impairment of nitric oxide biosynthesis with oxidative stress. We measured in 60 hypercholesterolemic patients and 20 controls plasma total sRAGE levels, urinary 8-iso-prostaglandin (PG) FZa excretion, and plasma levels of asymmetric dimethylarginine (ADMA). The effects of two structurally different statins (pravastatin and atorvastatin) on these parameters were analyzed in 20 hypercholesterolemic subjects free of vascular disease. Plasma sRAGE was significantly lower, ADMA and urinary 8-iso-PGF(2 alpha), were higher, in hypercholesterolemic versus normocholesterolemic patients. Patients on statin treatment with previous myocardial infarction had lower 8-iso-PGF(2 alpha), higher sRAGE, and unchanged ADMA levels compared to subjects free of vascular disease. On multivariate regression analysis only 8-iso-PGF(2 alpha), and ADMA predicted sRAGE levels. An 8-week treatment with either statin was associated with a significant reduction in urinary 8-iso-PGF(2 alpha),, whereas only atorvastatin raised sRAGE levels near to normal values, with no change in ADMA levels. sRAGE might serve as an endogenous protecting factor for accelerated atherosclerosis mediated by oxidative stress and endothelial dysfunction in hypercholesterolemia. (C) 2007 Elsevier Inc. All rights reserved.