p-Cresyl sulfate is associated with carotid arteriosclerosis in hemodialysis patients and promotes atherogenesis in apoE -/- mice
p-Cresyl sulfate is associated with carotid arteriosclerosis in hemodialysis patients and promotes atherogenesis in apoE -/- mice
复制标题
对甲酚硫酸盐与血液透析患者的颈动脉硬化有关，并促进 apoE -/- 小鼠的动脉粥样硬化形成
DOI：
10.1038/ki.2015.287
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发表时间：
2016-02-01
影响因子：
19.6
通讯作者：
Zhang, Rui Y.
中科院分区：
文献类型：
--
作者：
Jing, Ya J.;Ni, Jing W.;Zhang, Rui Y.
对甲酚硫酸盐（PCS）是慢性肾病患者心血管疾病的危险因素。在这里，我们测试了血液透析患者血清 PCS 水平是否与颈动脉粥样硬化的发生率和进展相关，并确定了潜在的机制。共有 200 名血液透析患者被分为有或无颈动脉粥样硬化斑块，并进行了 5 年的随访。研究发现，有颈动脉粥样硬化斑块的患者血清 PCS 水平高于无颈动脉粥样硬化斑块的患者，并且与随访期间斑块总面积的增加呈正相关。多元logistic回归和混合效应模型分析表明，血清PCS水平与颈动脉粥样硬化斑块的发生和进展独立相关。 PCS诱导内皮细胞和巨噬细胞中炎症因子和粘附分子的表达。此外，PCS 通过增加活性氧的产生，在体外和体内触发单核细胞与内皮细胞的相互作用。与对照组相比，灌胃产生的 PCS 水平增加促进了 5/6 肾切除的 apoE -/- 小鼠的动脉粥样硬化形成； NADPH 氧化酶抑制剂减弱的过程。因此，血清PCS水平升高与血液透析患者颈动脉粥样硬化的发生和进展相关，并通过增加活性氧的产生促进动脉粥样硬化形成。
p-Cresyl sulfate (PCS) is a risk factor of cardiovascular disease in patients with chronic kidney disease. Here we tested whether serum PCS levels were related to the rate and evolution of carotid atherosclerosis in hemodialysis patients and identified a potential mechanism. A total of 200 hemodialysis patients were categorized as with or without carotid atherosclerotic plaque and followed for 5 years. Serum PCS levels were found to be higher in patients with than without carotid atherosclerotic plaque and positively correlated with increased total plaque area during follow-up. Multiple logistic regression and mixed effects model analyses showed that serum PCS levels were independently associated with the incidence and progression of carotid atherosclerotic plaque. PCS induced inflammatory factor and adhesion molecule expression in endothelial cells and macrophages. In addition, PCS triggered monocyte-endothelial cell interaction in vitro and in vivo through increased production of reactive oxygen species. Compared with controls, increase of PCS levels produced by gavage promoted atherogenesis in 5/6-nephrectomized apoE -/- mice; a process attenuated by NADPH oxidase inhibitors. Thus, increased serum PCS levels are associated with the occurrence and progression of carotid atherosclerosis in hemodialysis patients and promote atherogenesis through increased reactive oxygen species production.