p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by targeting vascular smooth muscle cells
p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by targeting vascular smooth muscle cells
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对甲酚硫酸酯通过靶向血管平滑肌细胞促进动脉粥样硬化病变的形成并诱导斑块不稳定
DOI：
10.1007/s11684-016-0463-x
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发表时间：
2016-09-01
影响因子：
8.1
通讯作者：
Jin, Wei
中科院分区：
文献类型：
--
作者：
Han, Hui;Chen, Yanjia;Jin, Wei
冠状动脉粥样硬化是慢性肾脏疾病的主要并发症。这种情况导致透析患者的死亡率增加。对甲苯硫酸盐（PCS）是一种蛋白结合尿毒症毒素的原型，无法通过常规透析程序有效清除。在本研究中，将经历5/6肾切除术的ApoE-/-小鼠随机分为两组，即，媒介物处理组（n= 20）和PCS处理组（n= 20）。高脂饮食8周或24周后处死小鼠进行面部和免疫组织学分析。用磷酸盐缓冲液或500 μmol/L PCS处理大鼠主动脉血管平滑肌细胞（VSMCs）。PCS给药8周后，观察到PCS处理的小鼠遭受增加的动脉粥样硬化病变。此外，24周的PCS给药也明显增加了主动脉斑块的易损性指数。PCS也被观察到在疾病的进展过程中促进VSMCs的迁移和增殖。此外，PCS破坏了斑块内基质金属蛋白酶和金属蛋白酶组织抑制剂之间的平衡。因此，PCS可能通过靶向血管平滑肌细胞，在促进动脉粥样硬化形成和干扰斑块稳定性方面发挥重要作用。
Coronary atherosclerosis is a major complication of chronic kidney disease. This condition contributes to the increased mortality in dialysis patients.p-Cresyl sulfate (PCS) is a prototype of protein-bound uremic toxins that cannot be efficiently removed through routine dialysis procedures. In the present study, ApoE–/–mice that underwent 5/6 nephrectomy were randomly divided into two groups, namely, vehicle-treated group (n= 20) and PCS-treated group (n= 20). Mice were sacrificed for en face and immunohistological analyses after 8 or 24 weeks of high-fat diet. Rat aortic vascular smooth muscle cells (VSMCs) were treated with phosphate buffer solution or 500 μmol/L PCS forin vitroevaluation. PCS-treated mice were observed to suffer increased atherosclerotic lesions after eight weeks of PCS administration. Moreover, 24 weeks of PCS administration also markedly increased the vulnerability index of aortic plaques. PCS was also observed to facilitate the migration and proliferation of VSMCs during the progression of the disease. Moreover, PCS disturbed the balance between matrix metalloproteinases and tissue inhibitor of metalloproteinases within the plaques. Thus, PCS played a vital role in promoting atherogenesis and disturbing the stability of formed plaques probably by targeting VSMCs.