Document Detail


Insulin-like growth factor-I receptors in atherosclerotic plaques of symptomatic and asymptomatic patients with carotid stenosis: effect of IL-12 and IFN-gamma.
MedLine Citation:
PMID:  17040964     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The balance between apoptosis and survival of vascular smooth muscle cells (VSMCs) in the fibrous cap appears to best correlate with plaque instability or stability and is controlled by growth factors and cytokines. We recently reported the inhibition of insulin-like growth factor (IGF)-I-induced proliferation and increase in apoptosis of VSMCs by atheroma-associated cytokines. Here we assessed the expression of IGF-I receptor (IGF-IR) in atherosclerotic plaques and in plaque VSMCs of asymptomatic and symptomatic patients with carotid stenosis and examined the effect of IGF-I, IL-12, and IFN-gamma on the expression of IGF-IR and IGF-binding protein (IGFBP)-3 in plaque VSMCs. We observed significantly lower density of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic nuclei and increased positive immunoreactivity to IGF-IR and mRNA transcripts of endogenous IGF-I and IGF-IR in asymptomatic than in symptomatic plaque VSMCs. Positive correlation was found between apoptosis and IGF-IR expression in asymptomatic (r(2) = 0.942) and symptomatic (r(2) = 0.908) plaque VSMCs. The specific binding of (125)I-labeled IGF-I was 3.7-fold higher in plaque VSMCs of asymptomatic patients than in symptomatic patients. IGF-I increased both IGF-IR mRNA transcripts and expression of IGFBP-3 in VSMCs of asymptomatic plaques. IL-12 and IFN-gamma decreased IGF-IR mRNA transcripts and further increased the expression of IGFBP-3 in asymptomatic VSMCs but had no effect in symptomatic VSMCs. These data suggest that the decreased expression of IGF-IR mRNA and increased expression of IGFBP-3 in carotid plaques of symptomatic patients could be due to atheroma-associated cytokines and this could result in plaque instability.
Authors:
Guanghong Jia; Gang Cheng; Krish Soundararajan; Devendra K Agrawal
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2006-10-13
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  292     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-08     Completed Date:  2007-03-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1051-7     Citation Subset:  IM    
Affiliation:
Department of Biomedical Science, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Apoptosis
Carotid Artery Diseases / complications,  metabolism*,  pathology
Carotid Stenosis / etiology,  physiopathology*,  surgery
Cells, Cultured
Endarterectomy, Carotid
Female
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Insulin-Like Growth Factor Binding Proteins / metabolism*
Insulin-Like Growth Factor I / metabolism
Interferon-gamma / metabolism*,  pharmacology
Interleukin-12 / metabolism*,  pharmacology
Male
Muscle, Smooth, Vascular / metabolism
Myocytes, Smooth Muscle / metabolism
RNA, Messenger / metabolism
Receptor, IGF Type 1 / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
R01-HL-070885/HL/NHLBI NIH HHS; R01-HL-073349/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/IGFBP3 protein, human; 0/Insulin-Like Growth Factor Binding Proteins; 0/RNA, Messenger; 187348-17-0/Interleukin-12; 67763-96-6/Insulin-Like Growth Factor I; 82115-62-6/Interferon-gamma; EC 2.7.10.1/Receptor, IGF Type 1

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