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Title of article :
C-reactive protein induces endothelial cell apoptosis and matrix metalloproteinase-9 production in human mononuclear cells: Implications for the destabilization of atherosclerotic plaque
Author/Authors :
Aoi Nabata، نويسنده , , Masatoshi Kuroki، نويسنده , , Hiroto Ueba، نويسنده , , Shigemasa Hashimoto، نويسنده , , Tomio Umemoto، نويسنده , , Hiroshi Wada، نويسنده , , Takanori Yasu، نويسنده , , Muneyasu Saito، نويسنده , , Shin-ichi Momomura، نويسنده , , Masanobu Kawakami، نويسنده ,
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روزنامه با شماره پیاپی سال 2008
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Abstract :
C-reactive protein (CRP) has been suggested to directly induce the inflammatory response leading to the progression of atherosclerosis. However, recent in vitro studies raised the possibility that the effects of CRP are caused by biologically active contaminants such as sodium azide and endotoxin. In this study, we tested whether azide- and endotoxin-free CRP induces endothelial cell apoptosis and production of proinflammatory mediators. In human endothelial cells, CRP significantly inhibited cell proliferation and increased endothelial cell apoptosis evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and caspase-3 activity assay, which is reversed by a function-blocking antibody to FcgammaRIIIB by 78%. Western blot analysis showed that CRP significantly attenuated flow-mediated activation of Akt, a key molecule for endothelial cell survival pathways. In human mononuclear cells, CRP-induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and matrix metalloproteinase-9 (MMP-9) in a concentration-dependent manner. This CRP-induced MMP-9 production was significantly inhibited by function-blocking antibodies to TNF-alpha, IL-1beta, and FcgammaRIIA. These findings suggest that CRP itself induces endothelial cell apoptosis and production of proinflammatory mediators. Because endothelial cell apoptosis and MMP-9 production are critical for the destabilization of atherosclerotic plaque, this study may provide insight into a role of CRP in the development of plaque rupture.
Keywords :
C-reactive protein , matrix metalloproteinase , Apoptosis , endothelium , leukocytes
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