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Combined sub-optimal doses of Rosuvastatin and Bexarotene impairs angiotensin II-induced arterial mononuclear cell adhesion through inhibition of Nox5 signaling pathways and increased RXR/PPARα and RXR/PPARγ interactions

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Combined sub-optimal doses of Rosuvastatin and Bexarotene impairs angiotensin II-induced arterial mononuclear cell adhesion through inhibition of Nox5 signaling pathways and increased RXR/PPARα and RXR/PPARγ interactions

dc.contributor.author	Escudero, Paula
dc.contributor.author	Martinez de Marañón, Aranzazu
dc.contributor.author	Collado, Aida
dc.contributor.author	González Navarro, Herminia
dc.contributor.author	Hermenegildo, Carlos
dc.contributor.author	Peiró, Concepción
dc.contributor.author	Piqueras Ruiz, Laura
dc.contributor.author	Sanz Ferrando, María Jesús
dc.date.accessioned	2020-09-30T17:38:43Z
dc.date.available	2020-09-30T17:38:43Z
dc.date.issued	2015
dc.identifier.citation	Escudero, Paula Martinez de Marañón, Aranzazu Collado, Aida Gonzalez-Navarro, Herminia Hermenegildo, Carlos Peiró, Concepción Piqueras, Laura Sanz, Maria-Jesús 2015 Combined sub-optimal doses of Rosuvastatin and Bexarotene impairs angiotensin II-induced arterial mononuclear cell adhesion through inhibition of Nox5 signaling pathways and increased RXR/PPARα and RXR/PPARγ interactions Antioxidants & Redox Signaling 22 901 920
dc.identifier.uri	https://hdl.handle.net/10550/75710
dc.description.abstract	Aim: Mononuclear cell (MC) infiltration into the arterial subendothelium is a key event in atherogenesis. Rosuvastatin (Rosu) and bexarotene (Bex) exert anti-inflammatory activity, but serious dose-related adverse effects have emerged. The need for safer and effective strategies to prevent and treat atherosclerosis led us to test the effect of combined use of both drugs on angiotensin II (Ang-II)-induced arterial MC recruitment. Results: Vehicle, Rosu (10-30 nM), Bex (0.3-1 μM), or a combination of both were administered to human umbilical arterial endothelial cells (HUAECs) 20 h before stimulation with 1 μM Ang-II (4 h). Surprisingly, a combination of Rosu (10 nM)+Bex (0.3 μM), which did not influence Ang-II-induced MC recruitment when either stimulus was studied alone, significantly reduced this response. This effect was accompanied by diminished Ang-II-induced ICAM-1, VCAM-1, and CX3CL1 endothelial expression and CXCL1, CXCL8, CCL2, and CCL5 production. Preincubation of HUAECs with Rosu+Bex inhibited Nox5 expression and Nox5-induced RhoA activation stimulated by Ang-II through increased RXRα, PPARα, and PPARγ expression in addition to RXRα/PPARα and RXRα/PPARγ interactions. In vivo, combined but not single administration of Rosu (1.25 mg/kg/day) and Bex (10 mg/kg/day) significantly diminished Ang-II-induced arteriolar leukocyte adhesion in the cremasteric microcirculation of C57BL/6 mice and atherosclerotic lesion formation in apoE(-/-) mice subjected to an atherogenic diet. Innovation and conclusion: Combined administration of Bex+Rosu at suboptimal doses may constitute a new alternative and effective therapy in the control of the vascular inflammation associated to cardiometabolic disorders, since they synergize in their anti-inflammatory actions and may counteract their associated adverse effects.
dc.language.iso	eng
dc.relation.ispartof	Antioxidants & Redox Signaling, 2015, vol. 22, p. 901 -920
dc.subject	Sistema cardiovascular
dc.subject	Diabetis
dc.subject	Artèries
dc.title	Combined sub-optimal doses of Rosuvastatin and Bexarotene impairs angiotensin II-induced arterial mononuclear cell adhesion through inhibition of Nox5 signaling pathways and increased RXR/PPARα and RXR/PPARγ interactions
dc.type	journal article	es_ES
dc.date.updated	2020-09-30T17:38:43Z
dc.identifier.doi	10.1089/ars.2014.5969
dc.identifier.idgrec	108906
dc.rights.accessRights	open access	es_ES