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.
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。