Insulin-like growth factor-I receptors in atherosclerotic plaques of symptomatic and asymptomatic patients with carotid stenosis

Effect of IL-12 and IFN-γ

Guanghong Jia, Gang Cheng, Krish Soundararajan, Devendra K. Agrawal

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19 Citations (Scopus)

Abstract

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-γ 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 125I-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-γ 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number2
DOIs
StatePublished - Feb 2007

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IGF Type 1 Receptor
Carotid Stenosis
Atherosclerotic Plaques
Interleukin-12
Vascular Smooth Muscle
Smooth Muscle Myocytes
Somatomedins
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 3
Messenger RNA
Apoptosis
Cytokines
DNA Nucleotidylexotransferase
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

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title = "Insulin-like growth factor-I receptors in atherosclerotic plaques of symptomatic and asymptomatic patients with carotid stenosis: Effect of IL-12 and IFN-γ",
abstract = "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-γ 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 125I-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-γ 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.",
author = "Guanghong Jia and Gang Cheng and Krish Soundararajan and Agrawal, {Devendra K.}",
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T1 - Insulin-like growth factor-I receptors in atherosclerotic plaques of symptomatic and asymptomatic patients with carotid stenosis

T2 - Effect of IL-12 and IFN-γ

AU - Jia, Guanghong

AU - Cheng, Gang

AU - Soundararajan, Krish

AU - Agrawal, Devendra K.

PY - 2007/2

Y1 - 2007/2

N2 - 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-γ 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 125I-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-γ 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.

AB - 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-γ 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 125I-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-γ 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.

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JO - American Journal of Physiology - Heart and Circulatory Physiology

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