Document Detail


RAGE signaling mediates post-injury arterial neointima formation by suppression of liver kinase B1 and AMPK activity.
MedLine Citation:
PMID:  22552116     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Intima formation involves smooth muscle cell (SMC) proliferation and migration that ultimately drives arterial stenosis, thrombosis, and ischemia in atherosclerosis, hypertension, and arterial revascularization. Receptor for advanced glycation endproducts (RAGE) is a transmembrane signaling receptor implicated in diabetic renal and vascular complications, and post-injury intima formation, partly via Signal transducer and activator of transcription 3 (STAT3) activation. The metabolic super-regulator Adenosine monophosphate kinase (AMPK) inhibits SMC proliferation and intima formation. AMPK activation is promoted by liver kinase B1 (LKB1), and LKB1 inhibits STAT3 activation. Here, we tested the hypothesis that RAGE promotes arterial intima formation by modulating both LKB1 and AMPK.
METHODS AND RESULTS: RAGE ligands (the calgranulin S100A11, and glycated albumin) suppressed AMPK activation in conjunction with increased proliferation and migration of cultured SMCs. These effects were inhibited both by RAGE deficiency and by prior AMPK activation. In SMCs, RAGE ligands decreased LKB1 activity. Moreover, knockdown of both LKB1 and AMPK were associated with increased STAT3 phosphorylation levels. In response to murine carotid artery ligation, expression of RAGE and S100A11 increased, whereas AMPK and LKB1 activity decreased in situ. Conversely, LKB1 and AMPK activity increased in situ, and neointima formation was attenuated in Rage(-/-) mice.
CONCLUSION: The linkage of decreased LKB1 and AMPK activity with increased STAT3 in SMCs mediates the capacity of RAGE ligand-induced signaling to promote neointima formation in response to arterial injury.
Authors:
Weifang Yu; Ru Liu-Bryan; Stephanie Stevens; Jagadeesha K Damanahalli; Robert Terkeltaub
Related Documents :
7758586 - Phosphatidylcholine-phospholipase c mediates the induction of nerve growth factor in cu...
11282216 - Hwansodan protects pc12 cells against serum-deprivation-induced apoptosis via a mechani...
20190816 - Anaplastic lymphoma kinase activates the small gtpase rap1 via the rap1-specific gef c3...
16313516 - Recombinant prion protein induces rapid polarization and development of synapses in emb...
18726576 - Synthesis of o-phosphopeptides on solid phase.
7758586 - Phosphatidylcholine-phospholipase c mediates the induction of nerve growth factor in cu...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-04-11
Journal Detail:
Title:  Atherosclerosis     Volume:  222     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-09-20     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  417-25     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases / genetics,  metabolism*
Animals
Carotid Arteries / metabolism,  pathology
Carotid Artery Injuries / enzymology*,  genetics,  pathology
Cattle
Cell Movement
Cell Proliferation
Cells, Cultured
Disease Models, Animal
Down-Regulation
Enzyme Activation
Gene Knockdown Techniques
Ligands
Liver / enzymology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle, Smooth, Vascular / metabolism*,  pathology
Neointima
Phosphorylation
Protein Phosphatase 2 / metabolism
Protein-Serine-Threonine Kinases / genetics,  metabolism*
Receptors, Immunologic / deficiency,  genetics,  metabolism*
S100 Proteins / metabolism
STAT3 Transcription Factor / metabolism
Serum Albumin / metabolism
Signal Transduction
Grant Support
ID/Acronym/Agency:
AR1067966/AR/NIAMS NIH HHS; HL077360/HL/NHLBI NIH HHS; HL087252/HL/NHLBI NIH HHS; R01 HL077360/HL/NHLBI NIH HHS; R01 HL087252/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Ligands; 0/Receptors, Immunologic; 0/S100 Proteins; 0/STAT3 Transcription Factor; 0/Serum Albumin; 0/Stat3 protein, mouse; 0/advanced glycosylation end-product receptor; 0/glycosylated serum albumin; EC 2.7.1.-/Stk11 protein, mouse; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.1.3.16/Protein Phosphatase 2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Resveratrol inhibits neointimal formation after arterial injury through an endothelial nitric oxide ...
Next Document:  Dietary fatty acids and peripheral artery disease in adults.