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Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells

机译：辛伐他汀对硫酸吲哚酚诱导的内皮细胞活化的调节作用缺乏

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Aims: Endothelial dysfunction is a common manifestation of chronic kidney disease (CKD). The protein-bound uremic toxins have emerged as important factors associated with cardiovascular disease and the outcome of CKD. The effect of indoxyl sulfate (IS) on endothelial cells remains unclear. Main methods: Human umbilical endothelial cells (HUVEC) were incubated using IS at two concentrations: 100 μM and 1000 μM over two periods of time: 16 and 48 h. HUVEC were also pre-treated with simvastatin to examine its effect. RT-PCR was used to assess changes in the gene expression of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), Monocyte chemotactic protein-1 (MCP-1), E-selectin, and angiotensin receptor type 1 (AT1R). Protein abundance of the investigated molecules was assessed by immunoblotting. Key findings: Treatment with 100 μM IS for 16 h induced a 2-fold increase in the expression of ICAM-1, VCAM-1, and MCP-1. At a concentration of 1000 μM, there was a 2-3-fold increase. An extended treatment period at low concentrations was associated with a 2-3 fold increase and the increase of ICAM-1 and VCAM-1 was more prominent under high concentration. Results of immunoblotting confirmed an increase in the abundance of ICAM-1, VCAM-1 and MCP-1. No significant change was noted in E-selectin and AT1R according to concentration or treatment duration. Pre-treatment with simvastatin did not alter IS-induced changes. Significance: IS increased the expression of adhesion molecules of endothelial cells exhibiting a concentration and duration dependent pattern. Simvastatin did not demonstrate any effect on IS-associated endothelial activation.
机译：目的：内皮功能障碍是慢性肾脏疾病（CKD）的常见表现。结合蛋白的尿毒症毒素已成为与心血管疾病和CKD结局相关的重要因素。硫酸吲哚酚（IS）对内皮细胞的作用仍不清楚。主要方法：使用IS在两种浓度的100μM和1000μM浓度的人脐带内皮细胞（HUVEC）中孵育两个时间段：16和48 h。 HUVEC也用辛伐他汀预处理以检查其作用。使用RT-PCR评估细胞内细胞粘附分子1（ICAM-1），血管细胞粘附分子1（VCAM-1），单核细胞趋化蛋白1（MCP-1），E-选择素和1型血管紧张素受体（AT1R）。通过免疫印迹评估所研究分子的蛋白质丰度。关键发现：用100μMIS处理16小时可导致ICAM-1，VCAM-1和MCP-1的表达增加2倍。在1000μM的浓度下，增加了2-3倍。在低浓度下延长治疗时间会增加2-3倍，而在高浓度下ICAM-1和VCAM-1的增加更为明显。免疫印迹结果证实ICAM-1，VCAM-1和MCP-1的丰度增加。根据浓度或治疗持续时间，E-选择素和AT1R未见明显变化。辛伐他汀预处理不会改变IS引起的变化。意义：IS增加了内皮细胞黏附分子的表达，表现出浓度和持续时间依赖性。辛伐他汀对与IS相关的内皮细胞活化没有任何作用。

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