(Circulation. 1999;100:1369-1373.)
© 1999 American Heart Association, Inc.
Brief Rapid Communication |
Chlamydia pneumoniae Infection of Vascular Smooth Muscle and Endothelial Cells Activates NF-
B and Induces Tissue Factor and PAI-1 Expression
A Potential Link to Accelerated Arteriosclerosis
From the Max Delbrück Center for Molecular Medicine (R. Dechend, C.S., A.L.), Berlin; Medical University of Lübeck (M.M., J.G.), Institute for Medical Microbiology and Hygiene, Lübeck; and Charité, Humboldt University at Berlin (R. Dietz, D.C.G.), Franz-Volhard Clinic, Berlin, Germany.
Correspondence to Ralf Dechend, MD, Max Delbrück Center for Molecular Medicine, Robert Rössle Str 10, D-13122 Berlin, Germany. E-mail rdechend{at}mdc-berlin.de
Background—Recent reports link C. pneumoniae infection of arteriosclerotic lesions to the precipitation of acute coronary syndromes, which also feature tissue factor and plasminogen activator inhibitor 1 (PAI-1) overexpression. We investigated whether or not C. pneumoniae can induce thrombogenicity by upregulation of procoagulant proteins.
Methods and Results—Human vascular endothelial
and smooth muscle cells were infected with a strain of C.
pneumoniae isolated from an
arteriosclerotic coronary artery. Tissue
factor, PAI-1, and interleukin-6 expression was increased in infected
cells. Concomitantly, NF-
B was activated and IB
degraded. p50/p65 heterodimers were identified as the components
responsible for the NF-B activity.
Conclusions—These data provide evidence that C.
pneumoniae infection can induce procoagulant protein and
proinflammatory cytokine expression. This cellular response is
accompanied by activation of NF-B. Our results demonstrate how
C. pneumoniae infection may initiate acute
coronary syndromes.
Key Words: plasminogen activator inhibitor 1 • tissue factor • interleukins • arteriosclerosis • C. pneumoniae
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
C. Wahl, F. Oswald, U. Simnacher, S. Weiss, R. Marre, and A. Essig Survival of Chlamydia pneumoniae-Infected Mono Mac 6 Cells Is Dependent on NF-kappa B Binding Activity Infect. Immun., November 1, 2001; 69(11): 7039 - 7045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.C. Kaski and E.G. Zouridakis Inflammation, infection and acute coronary plaque events Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I10 - I15. [Abstract] [PDF]
|
|
|
|
|
|
G. Wang, Y. L. Siow, and K. O Homocysteine induces monocyte chemoattractant protein-1 expression by activating NF-{kappa}B in THP-1 macrophages Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2840 - H2847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 N. Hill-Kapturczak, L. Truong, V. Thamilselvan, G. A. Visner, H. S. Nick, and A. Agarwal Smad7-dependent Regulation of Heme Oxygenase-1 by Transforming Growth Factor-beta in Human Renal Epithelial Cells J. Biol. Chem., December 22, 2000; 275(52): 40904 - 40909. [Abstract] [Full Text] [PDF]
|
|