PMID- 25169989
OWN - NLM
STAT- MEDLINE
DCOM- 20150107
LR  - 20231213
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 86
IP  - 5
DP  - 2014 Nov
TI  - Activation of the retinoid X receptor modulates angiotensin II-induced smooth 
      muscle gene expression and inflammation in vascular smooth muscle cells.
PG  - 570-9
LID - 10.1124/mol.114.092163 [doi]
AB  - 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-alpha-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 (PPARalpha, PPARgamma, PPARdelta, 
      LXR, and FXR). Bexarotene had a greater effect on calponin reduction, MCP-1 
      inhibition, and p38 MAP kinase inhibition than any individual agonist. PPARgamma 
      knockout cells demonstrated blunted responses to bexarotene, indicating that 
      PPARgamma 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.
CI  - Copyright (c) 2014 by The American Society for Pharmacology and Experimental 
      Therapeutics.
FAU - Lehman, Allison M B
AU  - Lehman AM
AD  - Division 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).
FAU - Montford, John R
AU  - Montford JR
AD  - Division 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).
FAU - Horita, Henrick
AU  - Horita H
AD  - Division 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).
FAU - Ostriker, Allison C
AU  - Ostriker AC
AD  - Division 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).
FAU - Weiser-Evans, Mary C M
AU  - Weiser-Evans MC
AD  - Division 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).
FAU - Nemenoff, Raphael A
AU  - Nemenoff RA
AD  - Division 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).
FAU - Furgeson, Seth B
AU  - Furgeson SB
AD  - Division 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.
LA  - eng
GR  - T32 HL007171/HL/NHLBI NIH HHS/United States
GR  - K08-HL103774/HL/NHLBI NIH HHS/United States
GR  - 2P01-HL014985/HL/NHLBI NIH HHS/United States
GR  - P01 HL014985/HL/NHLBI NIH HHS/United States
GR  - R01 HL088643/HL/NHLBI NIH HHS/United States
GR  - UL1 TR001082/TR/NCATS NIH HHS/United States
GR  - T32 DK007135/DK/NIDDK NIH HHS/United States
GR  - K08 HL103774/HL/NHLBI NIH HHS/United States
GR  - T32-DK7135/DK/NIDDK NIH HHS/United States
GR  - 1R01-HL88643/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140828
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Actins)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Microfilament Proteins)
RN  - 0 (PPAR gamma)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 11128-99-7 (Angiotensin II)
RN  - A61RXM4375 (Bexarotene)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Actins/genetics/metabolism
MH  - Angiotensin II/genetics/*metabolism
MH  - Animals
MH  - Bexarotene
MH  - Calcium-Binding Proteins/genetics/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Gene Expression/drug effects/*genetics
MH  - Inflammation/*genetics/metabolism
MH  - MAP Kinase Signaling System/drug effects/genetics
MH  - Male
MH  - Microfilament Proteins/genetics/metabolism
MH  - Muscle, Smooth, Vascular/drug effects/*metabolism
MH  - Myocytes, Smooth Muscle/drug effects/*metabolism
MH  - PPAR gamma/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinoid X Receptors/*genetics/*metabolism
MH  - Signal Transduction/drug effects/genetics
MH  - Tetrahydronaphthalenes/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/genetics/metabolism
MH  - Calponins
PMC - PMC4201143
EDAT- 2014/08/30 06:00
MHDA- 2015/01/08 06:00
PMCR- 2015/11/01
CRDT- 2014/08/30 06:00
PHST- 2014/08/30 06:00 [entrez]
PHST- 2014/08/30 06:00 [pubmed]
PHST- 2015/01/08 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - mol.114.092163 [pii]
AID - MOL_092163 [pii]
AID - 10.1124/mol.114.092163 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2014 Nov;86(5):570-9. doi: 10.1124/mol.114.092163. Epub 2014 Aug 
      28.