Abstract
Emerging evidence demonstrates that high plasma C-reactive protein (CRP) levels or low plasma insulin-like growth factor 1 (IGF-1) concentrations may be separately associated with the increased risk of coronary artery disease or myocardial infarction. Interestingly, animal model studies and epidemiological investigations indicate that circulating IGF-1 and CRP levels have an inverse correlation. The present study aims to evaluate if IGF-1 can directly oppose the effects of CRP on endothelial cell (EC) activation. We found that IGF-1 rescues endothelial nitric oxide synthase activity and decreases the release of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 from ECs. We also showed that IGF-1 antagonizes the effects of CRP by activating the PI3K/Akt pathway and suppressing the JNK/c-Jun and MAPK p38/ATF2 signaling pathways, rather than inhibiting ERK1/2 activity. These findings provide evidence of the physiopathological mechanisms of endothelial activation and novel insights into the protective properties of IGF-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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C-Reactive Protein / pharmacology*
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Coronary Vessels / cytology
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Cytoprotection / drug effects
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Endothelial Cells / drug effects
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Endothelial Cells / enzymology
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Endothelial Cells / metabolism*
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Enzyme Activation / drug effects
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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Insulin-Like Growth Factor I / pharmacology*
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JNK Mitogen-Activated Protein Kinases / metabolism
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Nitric Oxide Synthase Type III / metabolism
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Phosphatidylinositol 3-Kinase / metabolism
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-akt / metabolism
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Proto-Oncogene Proteins c-jun / metabolism
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Signal Transduction / drug effects
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Proto-Oncogene Proteins c-jun
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Insulin-Like Growth Factor I
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C-Reactive Protein
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NOS3 protein, human
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Nitric Oxide Synthase Type III
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Phosphatidylinositol 3-Kinase
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases