Abstract
Th17 cells producing IL-17 are involved in the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. In this study, we investigated the effects of IL-17 on human vascular endothelial cells and showed that IL-17 induced cell death of the vascular endothelial cells, which played a pivotal role in plaque destabilization triggering acute coronary syndrome (ACS). We showed that circulating Th17 cells and IL-17 increased in patients with ACS compared to the patients with stable angina or health individuals; the plasma levels of IL-6 increased but TGF-β decreased in ACS patients, exhibiting a positive and negative correlation with that of IL-17, respectively. Importantly, we uncovered that IL-17 promoted the production of von Willebrand factor by endothelial cells and induced endothelial apoptosis by activating caspase-3, caspase-9 and up-regulating the ratio of Bax/Bcl-2, indicating the function of IL-17 in vascular endothelial damage as a potential mechanism for the pathogenesis of human ACS.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Coronary Syndrome / immunology*
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Acute Coronary Syndrome / metabolism
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Acute Coronary Syndrome / pathology
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Angina, Stable / immunology
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Angina, Stable / metabolism
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Apoptosis / drug effects*
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Caspase 3 / biosynthesis
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Caspase 3 / genetics
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Caspase 9 / biosynthesis
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Caspase 9 / genetics
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Cells, Cultured / drug effects
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Cells, Cultured / metabolism
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Coronary Artery Disease / immunology
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Coronary Artery Disease / metabolism
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Coronary Artery Disease / pathology
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Endothelial Cells / pathology
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Female
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Gene Expression Regulation / drug effects*
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Humans
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Interleukin-17 / blood
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Interleukin-17 / pharmacology
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Interleukin-17 / physiology*
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Interleukin-6 / blood
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Male
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Middle Aged
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Recombinant Proteins / pharmacology
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Th17 Cells / immunology*
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Transforming Growth Factor beta / blood
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Up-Regulation / drug effects
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bcl-2-Associated X Protein / biosynthesis
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bcl-2-Associated X Protein / genetics
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von Willebrand Factor / biosynthesis*
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von Willebrand Factor / genetics
Substances
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BAX protein, human
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IL17A protein, human
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IL6 protein, human
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Interleukin-17
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Interleukin-6
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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Transforming Growth Factor beta
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bcl-2-Associated X Protein
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von Willebrand Factor
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CASP3 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 9