atorvastatin’s therapeutic potential in atherosclerosis: inhibiting tgf-β-induced proteoglycan glycosaminoglycan chain elongation through ros-erk1/2-smad2l signaling pathway modulation in vascular smooth muscle cells

Objective: according to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to thedeposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongatedglycosaminoglycan (gag) chains. recent studies have elucidated a signaling pathway whereby transforming growthfactor-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 knownto exhibit pleiotropic effects, including antioxidant and anti-inflammatory. the purpose of the present research wasto ascertain the influence of atorvastatin on tgf-β-stimulated expression of chst11 and chsy1 and associatedsignaling pathways using an in vitro model.materials and methods: in this experimental study, vascular smooth muscle cells (vsmcs) were pre-incubatedwith atorvastatin (0.1-10 μm) prior to being stimulated with tgf-β (2 ng/ml). the experiment aimed to evaluate thephosphorylation levels of smad2c, smad2l, erk1/2, the nox p47phox subunit, ros production, and the mrnaexpression of chst11 and chsy1.results: our research results indicated that atorvastatin inhibited tgf-β-stimulated chsy1 and chst11 mrnaexpression. further experiments showed that atorvastatin diminished tgf-β-stimulated ros production and weakenedtgf-β-stimulated phosphorylation of p47phox, erk1/2, and smad2l; however, we observed no effect on the tgf-β-smad2c pathway.conclusion: these data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulationof the ros-erk1/2-smad2l signaling pathway. this provides valuable insight into the potential mechanisms by whichatorvastatin exerts its pleiotropic effects against atherosclerosis.