| In Vitro | In vitro activity: Atorvastatin inhibits pre-proET-1 mRNA expression in a concentration- and time-dependent fashion (60-70% maximum inhibition) and reduces immunoreactive ET-1 levels (25-50%), this inhibitory effect is maintained in the presence of oxidized LDL (1-50 mg/mL). Atorvastatin significantly reduces angiotensin II-induced and epidermal growth factor-induced ROS production in VSMCs. Atorvastatin downregulates mRNA expression of the NAD(P)H oxidase subunit nox1 in VSMCs, whereas p22phox mRNA expression is not significantly altered. Atorvastatin inhibits membrane translocation of rac1 GTPase, which is required for the activation of NAD(P)H oxidase. Atorvastatin (0.1 μM) significantly diminishes NF-κB activation induced by Ang II and TNF-α in mononuclear cells and VSMC. Atorvastatin (1 μM) diminishes MCP-1 expression induced by Ang II, TNF-α and is reversed by Mevalonate only in Ang II-stimulated cells. Atorvastatin (1 μM) diminishes IP-10 expression induced by Ang II and by TNF-α in VSMC, and this reduction is partially reversed by Mevalonate. Atorvastatin and Gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation. |
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