Evidence map›Paper›PMID 25169989›Full record

ArticleMolecular pharmacology2014

Activation of the retinoid X receptor modulates angiotensin II-induced smooth muscle gene expression and inflammation in vascular smooth muscle cells.

Allison M B Lehman, John R Montford, Henrick Horita, Allison C Ostriker, Mary C M Weiser-Evans, Raphael A Nemenoff, Seth B Furgeson

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Proinflammation, profibrosis, and arterial aging.Aging medicine (Milton (N.S.W)) · 2020
    Review
  7. Article
  8. Article
  9. Cytosolic phospholipase AProstaglandins & other lipid mediators · 2016
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Allison M B LehmanDivision of Renal Diseases and Hypertension (A.L., J.R.M., H.H., A.C.O., M.W.E., R.A.N., S.B.F.), Cardiovascular Pulmonary Research Laboratory, Department of Medicine (M.W.E., R.A.N.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; and Department of Medicine, Denver Health Hospital, Denver, Colorado (S.B.F).
John R MontfordDivision of Renal Diseases and Hypertension (A.L., J.R.M., H.H., A.C.O., M.W.E., R.A.N., S.B.F.), Cardiovascular Pulmonary Research Laboratory, Department of Medicine (M.W.E., R.A.N.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; and Department of Medicine, Denver Health Hospital, Denver, Colorado (S.B.F).
Henrick HoritaDivision of Renal Diseases and Hypertension (A.L., J.R.M., H.H., A.C.O., M.W.E., R.A.N., S.B.F.), Cardiovascular Pulmonary Research Laboratory, Department of Medicine (M.W.E., R.A.N.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; and Department of Medicine, Denver Health Hospital, Denver, Colorado (S.B.F).
Allison C OstrikerDivision of Renal Diseases and Hypertension (A.L., J.R.M., H.H., A.C.O., M.W.E., R.A.N., S.B.F.), Cardiovascular Pulmonary Research Laboratory, Department of Medicine (M.W.E., R.A.N.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; and Department of Medicine, Denver Health Hospital, Denver, Colorado (S.B.F).
Mary C M Weiser-EvansDivision of Renal Diseases and Hypertension (A.L., J.R.M., H.H., A.C.O., M.W.E., R.A.N., S.B.F.), Cardiovascular Pulmonary Research Laboratory, Department of Medicine (M.W.E., R.A.N.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; and Department of Medicine, Denver Health Hospital, Denver, Colorado (S.B.F).
Raphael A NemenoffDivision of Renal Diseases and Hypertension (A.L., J.R.M., H.H., A.C.O., M.W.E., R.A.N., S.B.F.), Cardiovascular Pulmonary Research Laboratory, Department of Medicine (M.W.E., R.A.N.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; and Department of Medicine, Denver Health Hospital, Denver, Colorado (S.B.F).
Seth B FurgesonDivision of Renal Diseases and Hypertension (A.L., J.R.M., H.H., A.C.O., M.W.E., R.A.N., S.B.F.), Cardiovascular Pulmonary Research Laboratory, Department of Medicine (M.W.E., R.A.N.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; and Department of Medicine, Denver Health Hospital, Denver, Colorado (S.B.F) seth.furgeson@ucdenver.edu.
University of Colorado Denver · USDenver Health Medical Center · USUniversity of Colorado Anschutz Medical Campus · US

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
VRAC and Rho in pulmonary EC proliferationP01HL014985 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI STENMARK, KURT R. · 1985 to 2019
$35.1M
Translational Pulmonary Vascular Biology ProgramT32HL007171 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Sonia Castro Flores, Tim Lahm · 1985 to 2026
$9.4M
TRAINING IN RENAL &ELECTROLYTE DISEASE &HYPERTENSIONT32DK007135 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI JOHNSON, RICHARD JOSEPH, KENDRICK, JESSICA B · 1986 to 2024
$5.3M
Role of PTEN in Vascular Lesion FormationR01HL088643 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI WEISER-EVANS, MARY CM. · 2009 to 2012
$1.5M
The role of smooth muscle PPAR gamma in neointima formationK08HL103774 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI FURGESON, SETH BERNAT · 2011 to 2015
$652k
NCATS NIH HHS UL1 TR001082NHLBI NIH HHS 1R01-HL88643NHLBI NIH HHS 2P01-HL014985NHLBI NIH HHS K08 HL103774NHLBI NIH HHS K08-HL103774NHLBI NIH HHS P01 HL014985NHLBI NIH HHS R01 HL088643NHLBI NIH HHS T32 HL007171NIDDK NIH HHS T32 DK007135NIDDK NIH HHS T32-DK7135
6 · The paper itself

Abstract

The retinoid X receptor (RXR) partners with numerous nuclear receptors, such as the peroxisome proliferator activated receptor (PPAR) family, liver X receptors (LXRs), and farnesoid X receptor (FXR). Although each heterodimer can be activated by specific ligands, a subset of these receptors, defined as permissive nuclear receptors, can also be activated by RXR agonists known as rexinoids. Many individual RXR heterodimers have beneficial effects in vascular smooth muscle cells (SMCs). Because rexinoids can potently activate multiple RXR pathways, we hypothesized that treating SMCs with rexinoids would more effectively reverse the pathophysiologic effects of angiotensin II than an individual heterodimer agonist. Cultured rat aortic SMCs were pretreated with either an RXR agonist (bexarotene or 9-cis retinoic acid) or vehicle (dimethylsulfoxide) for 24 hours before stimulation with angiotensin II. Compared with dimethylsulfoxide, bexarotene blocked angiotensin II-induced SM contractile gene induction (calponin and smooth muscle-α-actin) and protein synthesis ([(3)H]leucine incorporation). Bexarotene also decreased angiotensin II-mediated inflammation, as measured by decreased expression of monocyte chemoattractant protein-1 (MCP-1). Activation of p38 mitogen-activated protein (MAP) kinase but not extracellular signal-related kinase (ERK) or protein kinase B (Akt) was also blunted by bexarotene. We compared bexarotene to five agonists of nuclear receptors (PPARα, PPARγ, PPARδ, LXR, and FXR). Bexarotene had a greater effect on calponin reduction, MCP-1 inhibition, and p38 MAP kinase inhibition than any individual agonist. PPARγ knockout cells demonstrated blunted responses to bexarotene, indicating that PPARγ is necessary for the effects of bexarotene. These data demonstrate that RXR is a potent modulator of angiotensin II-mediated responses in the vasculature, partially through inhibition of p38.

Indexed as

ActinsAngiotensin IIAnimalsBexaroteneCalcium-Binding ProteinsCalponinsCells, CulturedChemokine CCL2Gene ExpressionInflammationMaleMAP Kinase Signaling SystemMicrofilament ProteinsMuscle, Smooth, VascularMyocytes, Smooth Musclep38 Mitogen-Activated Protein KinasesActinsAngiotensin IIBexaroteneCalcium-Binding ProteinsCalponinsCcl2 protein, ratChemokine CCL2Microfilament Proteinsp38 Mitogen-Activated Protein KinasesPPAR gammaProto-Oncogene Proteins c-aktRetinoid X ReceptorsTetrahydronaphthalenes

Identifiers

PMID25169989
PMCPMC4201143
OpenAlexW2121946348

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.