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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…

Overview of attention for article published in Antioxidants & Redox Signaling, January 2015
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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.
Published in
Antioxidants & Redox Signaling, January 2015
DOI 10.1089/ars.2014.5969
Pubmed ID
Authors

Paula Escudero, Aranzazu Martinez de Marañón, Aida Collado, Herminia Gonzalez-Navarro, Carlos Hermenegildo, Concepcion Peiró, Laura Piqueras, Maria J Sanz

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) 20h prior to stimulation with 1 μM Ang-II (4h). 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 RXRalpha, PPARalpha and PPARgamma expression in addition to RXRalpha/PPARalpha and RXRalpha/PPARgamma 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.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 5%
Unknown 20 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 29%
Student > Master 3 14%
Student > Bachelor 2 10%
Professor 2 10%
Researcher 2 10%
Other 3 14%
Unknown 3 14%
Readers by discipline Count As %
Medicine and Dentistry 8 38%
Biochemistry, Genetics and Molecular Biology 5 24%
Pharmacology, Toxicology and Pharmaceutical Science 2 10%
Chemical Engineering 1 5%
Agricultural and Biological Sciences 1 5%
Other 1 5%
Unknown 3 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 January 2015.
All research outputs
#12,290,140
of 20,585,116 outputs
Outputs from Antioxidants & Redox Signaling
#993
of 1,777 outputs
Outputs of similar age
#153,047
of 315,987 outputs
Outputs of similar age from Antioxidants & Redox Signaling
#13
of 29 outputs
Altmetric has tracked 20,585,116 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,777 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 315,987 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.