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Title: [Quercetin attenuates Ox-LDL-induced calcification in vascular smooth muscle cells by regulating ROS-TLR4 signaling pathway].
Author: Liang Q, Chen Y, Li C, Lu L.
Journal: Nan Fang Yi Ke Da Xue Xue Bao; 2018 Jul 30; 38(8):980-985. PubMed ID: 30187880.
Abstract:
OBJECTIVE: To determine whether quercetin inhibits oxidized low-density lipoprotein (Ox-LDL)-induced osteogenic differentiation and calcification of vascular smooth muscle cells (VSMCs) and understand the underlying mechanism. METHODS: The calcification of human VSMCs following Ox-LDL treatment was assessed using alizarin red staining and by detecting ALP activity. The mRNA expressions of the bone-related genes including Msx2, BMP2 and Osterix, and the contractile proteins including SMA and SM22a were analyzed using qPCR. The effects of quercetin were investigated on OxLDL-induced VSMC calcification and changes in ALP activity, expressions of Msx2, BMP2, Osterix, SMA and SM22a, ROS levels and SOD activity. The effect of Toll like receptor 4 (TLR4) silencing mediated by siRNA transfection on cell calcification, ALP activity, gene expressions and ROS levels were investigated. RESULTS: Ox-LDL treatment promoted VSMC calcification and up-regulated TLR4 expression. Quercetin treatment significantly attenuated Ox-LDL-induced VSMC calcification, reduced ALP activity, down-regulated the expression levels of Msx2, BMP2 and Osterix, and up-regulated the expressions of vascular smooth muscle contractile proteins SMA and SM22a. In addition, Quercetin treatment markedly increased SOD activity, reduced ROS levels and TLR4 expression in VSMCs. Silencing TLR4 expression using TLR4 siRNA also significantly decreased calcification of the VSMCs. CONCLUSIONS: Quercetin inhibits Ox-LDL-induced VSMC calcification in VSMCs possibly by targeting the ROS/TLR4 signaling pathway. 目的: 观察槲皮素对氧化型低密度脂蛋白（Ox-LDL）诱导的血管平滑肌细胞成骨样分化和钙化的作用，并阐明其分子机制。方法: 采用Ox-LDL处理人血管平滑肌细胞，茜素红染色检测细胞钙化，测定碱性磷酸酶（ALP）活性和qPCR测骨相关蛋白Msx2、BMP2、Osterix以及收缩蛋白SMA和SM22α mRNA表达水平。观察槲皮素对Ox-LDL诱导的血管平滑肌细胞钙化，ALP活性，TLR4、Msx2、BMP2、Osterix、SMA和SM22α的mRNA表达水平，ROS含量及SOD活性的影响。采用TLR4 siRNA转染血管平滑肌细胞，观察敲低TLR4对细胞钙化，ALP活性及Msx2、BMP2、Osterix、SMA和SM22α mRNA表达水平的影响。结果: Ox-LDL可促进血管平滑肌细胞钙化和上调TLR4表达水平（P < 0.05）；槲皮素能明显减轻Ox-LDL诱导的细胞钙化和降低ALP的活性，下调Msx2、BMP2、Osterix mRNA的表达水平，上调血管平滑肌收缩蛋白SMA和SM22α mRNA的表达水平（P < 0.05）。此外，槲皮素可明显提高SOD的活性，降低活性氧物质（ROS）的含量，下调TLR4的表达水平（P < 0.05）；TLR4 siRNA也能减轻Ox-LDL诱导的细胞钙化（P < 0.05）。结论: 槲皮素可明显抑制Ox-LDL诱导的血管平滑肌细胞钙化，其机制可能与ROS激活的TLR4信号通路有关。

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