Atorvastatin inhibits pro-inflammatory actions of aldosterone in vascular smooth muscle cells by reducing oxidative stress

Autor(es)

Bruder-Nascimento, Thiago ^{[1, 2, 3]} ; Callera, Glaucia E. ^[2] ; Montezano, Augusto C. ^{[4, 2]} ; de Chantemele, Eric J. Belin ^[3] ; Tostes, Rita C. ^[1] ; Touyz, Rhian M. ^{[4, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Sao Paulo - Brazil

^[2] Univ Ottawa, Kidney Res Ctr, Ottawa, ON - Canada

^[3] Augusta Univ, Med Coll Georgia, Vasc Biol Ctr, Augusta, GA - USA

^[4] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark - Scotland

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 221, p. 29-34, MAR 15 2019.
• Citações Web of Science: 0

Resumo

Vascular inflammatory responses play an important role in several cardiovascular diseases. Of the many proinflammatory 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 mu M 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. (AU)

• Processo FAPESP: 10/52214-6 - Contribuição do estresse oxidativo e enzimas NADPH oxidases (NOXes) para as lesões vasculares e renais associadas ao diabetes
• Beneficiário: Rita de Cassia Aleixo Tostes Passaglia
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/22035-5 - Contribuição do estresse oxidativo e enzimas NADPH oxidases (NOXes) para as lesões vasculares associadas ao diabetes: estudo em camundongos nocautes
• Beneficiário: Thiago Bruder Do Nascimento
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 11/01785-6 - Contribuição do estresse oxidativo e enzimas NADPH oxidases (NOXes) para as lesões vasculares associadas ao diabetes
• Beneficiário: Thiago Bruder Do Nascimento
• Modalidade de apoio: Bolsas no Brasil - Doutorado