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

Bruder-Nascimento, T., Callera, G. E., Montezano, A. C., Belin de Chantemele, E. J., Tostes, R. C. and Touyz, R. M. (2019) Atorvastatin inhibits pro-inflammatory actions of aldosterone in vascular smooth muscle cells by reducing oxidative stress. Life Sciences, 221, pp. 29-34. (doi:10.1016/j.lfs.2019.01.043) (PMID:30721707)

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Abstract

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 (100 nM) 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.

Item Type:Articles
Additional Information:This work was supported by the São Paulo Research Foundation[grant numbers 2010/52214-6 (to R.C.T); 2011/01785-6; 2011/22035-5 (to T.B.-N.)]; Coordination for the Improvement of Higher EducationPersonnel (CAPES) [grant number: 88887.092495/2015-00 (to T.B.-N)]; the Agence Universitaire de la Francophonie [grant number58145FT103]; the Juvenile Diabetes Research Foundation [grantnumber4-2010-528]; the Canadian Institutes of Health Research [grantnumber 44018]; and the British Heart Foundation [grant number CH/12/429762].
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Montezano, Dr Augusto and Touyz, Professor Rhian
Authors: Bruder-Nascimento, T., Callera, G. E., Montezano, A. C., Belin de Chantemele, E. J., Tostes, R. C., and Touyz, R. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Life Sciences
Publisher:Elsevier
ISSN:0024-3205
ISSN (Online):1879-0631
Published Online:02 February 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Life Sciences 221: 29-34
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607382Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)RG/13/7/30099RI CARDIOVASCULAR & MEDICAL SCIENCES