Atorvastatin inhibits pro-inflammatory actions of aldosterone in vascular smooth muscle cells by reducing oxidative stress
| Autor: | Thiago, Bruder-Nascimento, Glaucia E, Callera, Augusto C, Montezano, Eric J, Belin de Chantemele, Rita C, Tostes, Rhian M, Touyz |
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| Rok vydání: | 2018 |
| Předmět: |
Male
rac1 GTP-Binding Protein Redox signaling Myocytes Smooth Muscle Rats Inbred WKY Antioxidants Muscle Smooth Vascular Article Vascular Mineralocorticoids Atorvastatin Animals Aldosterone Cells Cultured Inflammation Angiotensin II Statins nutritional and metabolic diseases NADPH Oxidases Rats rac GTP-Binding Proteins Oxidative Stress lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Reactive Oxygen Species Oxidation-Reduction Signal Transduction |
| Zdroj: | Life sciences |
| ISSN: | 1879-0631 |
| Popis: | Vascular inflammatory responses play an important role in several cardiovascular diseases. Of the many pro-inflammatory vasoactive factors implicated in this process, is aldosterone, an important mediator of vascular oxidative stress. Statins, such as atorvastatin, are cholesterol-lowering drugs that have pleiotropic actions, including anti-oxidant properties independently of their cholesterol-lowering effect. This study investigated whether atorvastatin prevents aldosterone-induced VSMC inflammation by reducing reactive oxygen species (ROS) production. Vascular smooth muscle cells (VSMC) from WKY rats were treated with 1 μM atorvastatin for 60 min or for 72 h prior to aldosterone (10−7 mol/L) stimulation. Atorvastatin inhibited Rac1/2 and p47phox translocation from the cytosol to the membrane, as well as reduced aldosterone-induced ROS production. Atorvastatin also attenuated aldosterone-induced vascular inflammation and macrophage adhesion to VSMC. Similarly EHT1864, a Rac1/2 inhibitor, and tiron, ROS scavenger, reduced macrophage adhesion. Through its inhibitory effects on Rac1/2 activation and ROS production, atorvastatin reduces vascular ROS generation and inhibits VSMC inflammation. Our data suggest that in conditions associated with aldosterone-induced vascular damage, statins may have vasoprotective effects by inhibiting oxidative stress and inflammation. |
| Databáze: | OpenAIRE |
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