PDF(Pubmed)
Abstract：
OBJECTIVE: According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-β (TGF-β) promotes the expression of genes linked to proteoglycan GAG chain elongation (CHSY1 and CHST11) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research was to ascertain the influence of atorvastatin on TGF-β-stimulated expression of CHSY1 and CHST11 and associated signaling pathways using an in vitro model.
METHODS: In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of CHST11 and CHSY1.
RESULTS: Our research results indicated that atorvastatin inhibited TGF-β-stimulated CHSY1 and CHST11 mRNA expression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakened TGF-β-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-β- Smad2C pathway.
CONCLUSIONS: These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.
METHODS: In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of CHST11 and CHSY1.
RESULTS: Our research results indicated that atorvastatin inhibited TGF-β-stimulated CHSY1 and CHST11 mRNA expression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakened TGF-β-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-β- Smad2C pathway.
CONCLUSIONS: These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.
摘要：
目标：根据对保留的反应假设，动脉粥样硬化的开始归因于脂蛋白在动脉内膜中的沉积和保留，由具有超长糖胺聚糖（GAG）链的蛋白聚糖改变促进。最近的研究已经阐明了一种信号通路，通过该信号通路，转化生长因子-β（TGF-β）通过活性氧（ROS）和ERK1/2的下游磷酸化来促进与蛋白聚糖GAG链延长（CHSY1和CHST11）连接的基因的表达和Smad2L。已知阿托伐他汀表现出多效作用，包括抗氧化剂和抗炎。本研究的目的是使用体外模型确定阿托伐他汀对TGF-β刺激的CHSY1和CHST11表达及相关信号通路的影响。
方法：在本实验研究中，将血管平滑肌细胞(VSMC)与阿托伐他汀(0.1-10μM)预孵育,然后用TGF-β(2ng/ml)刺激.该实验旨在评估Smad2C的磷酸化水平，Smad2L,ERK1/2，即NOXp47phox亚基，ROS生产，CHST11和CHSY1的mRNA表达。
结果：我们的研究结果表明阿托伐他汀抑制TGF-β刺激的CHSY1和CHST11mRNA的表达。进一步的实验表明，阿托伐他汀减少了TGF-β刺激的ROS产生，并削弱了TGF-β刺激的p47phox磷酸化，ERK1/2和Smad2L；然而，我们观察到对TGF-β-Smad2C通路没有影响。
结论：这些数据表明，阿托伐他汀通过调节ROS-ERK1/2-Smad2L信号通路表现出抗动脉粥样硬化特性。这为阿托伐他汀发挥其多效性抗动脉粥样硬化作用的潜在机制提供了有价值的见解。
方法：在本实验研究中，将血管平滑肌细胞(VSMC)与阿托伐他汀(0.1-10μM)预孵育,然后用TGF-β(2ng/ml)刺激.该实验旨在评估Smad2C的磷酸化水平，Smad2L,ERK1/2，即NOXp47phox亚基，ROS生产，CHST11和CHSY1的mRNA表达。
结果：我们的研究结果表明阿托伐他汀抑制TGF-β刺激的CHSY1和CHST11mRNA的表达。进一步的实验表明，阿托伐他汀减少了TGF-β刺激的ROS产生，并削弱了TGF-β刺激的p47phox磷酸化，ERK1/2和Smad2L；然而，我们观察到对TGF-β-Smad2C通路没有影响。
结论：这些数据表明，阿托伐他汀通过调节ROS-ERK1/2-Smad2L信号通路表现出抗动脉粥样硬化特性。这为阿托伐他汀发挥其多效性抗动脉粥样硬化作用的潜在机制提供了有价值的见解。
