Department of Cardiology, Shanghai First People's Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai, PR China.
Mol Med Rep. 2012 Oct;6(4):774-8. doi: 10.3892/mmr.2012.1010. Epub 2012 Jul 27.
Matrix metalloproteinases (MMPs) are critical to vascular smooth muscle cell migration in vivo. The dysregulation of MMPs is involved in the pathogenesis of abnormal arterial remodeling, aneurysm formation and atherosclerotic plaque instability. It has been confirmed that lipopolysaccharides (LPS) constitute a strong risk factor for the development of atherosclerosis. In this study, we aimed to determine a potential mechanism of LPS on MMP-9 expression in human arterial smooth muscle cells (HASMCs). RT-PCR analysis was used to detect MMP-9 mRNA expression and western blot analysis was performed to examine MMP-9 protein expression. An electrophoretic mobility shift assay was also employed to determine NF-κB binding activity. Results showed that LPS induced MMP-9 mRNA and protein expression in HASMCs in a TLR4-dependent manner. Notably, upon blocking the NF-κB binding with pyrrolidine dithiocarbamate, it was demonstrated that the expression of MMP-9 by LPS occurs through TLR4/NF-κB pathways. It was concluded that LPS induced MMP-9 expression through the TLR4/NF-κB pathway. Thus, the TLR4/NF-κB pathway may be involved in the pathogenesis of atherosclerosis.
基质金属蛋白酶(MMPs)在血管平滑肌细胞的体内迁移中起着关键作用。MMPs 的失调参与了异常动脉重塑、动脉瘤形成和动脉粥样硬化斑块不稳定的发病机制。已经证实,脂多糖(LPS)是动脉粥样硬化发展的一个强有力的危险因素。在这项研究中,我们旨在确定 LPS 对人动脉平滑肌细胞(HASMCs)中 MMP-9 表达的潜在机制。使用 RT-PCR 分析检测 MMP-9 mRNA 表达,并用 Western blot 分析检测 MMP-9 蛋白表达。还进行了电泳迁移率变动分析以确定 NF-κB 结合活性。结果表明,LPS 以 TLR4 依赖的方式诱导 HASMCs 中 MMP-9 mRNA 和蛋白的表达。值得注意的是,用吡咯烷二硫代氨基甲酸盐阻断 NF-κB 结合后,证明 LPS 通过 TLR4/NF-κB 途径诱导 MMP-9 的表达。结论是 LPS 通过 TLR4/NF-κB 途径诱导 MMP-9 表达。因此,TLR4/NF-κB 途径可能参与了动脉粥样硬化的发病机制。