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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: Life Sciences; v. 221, p. 29-34, MAR 15 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 10/52214-6 - Contribution of oxidative stress and NOXes to diabetes-associated vascular and renal injury
• Grantee: Rita de Cassia Aleixo Tostes Passaglia
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/22035-5 - Contribution of oxidative stress and NADPH oxidase (NOXes) diabetes-associated vascular injury: study in knockout mice
• Grantee: Thiago Bruder Do Nascimento
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 11/01785-6 - Contribution of oxidative stress and NOXes to diabetes-associated vascular injury
• Grantee: Thiago Bruder Do Nascimento
• Support Opportunities: Scholarships in Brazil - Doctorate