Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo.
Atherosclerosis is characterized by inflammation and proliferation of vascular cells. The intracellular bacterium Chlamydia (Chlamydophila) pneumoniae uses blood monocytes [peripheral blood mononuclear cells (PBMCs)] for dissemination, has been found to persist in atherosclerotic lesions, and has been implicated in atherogenesis by small GTPase activation and T lymphocyte recruitment. Infection of human coronary artery smooth muscle cells with C. pneumoniae significantly induced mRNA and protein for the angiogenic transcription factor Egr-1, resulting in enhanced coronary artery smooth muscle cell proliferation, which was reduced by transfection with small interfering RNA duplexes targeted at Egr-1 mRNA. These effects required viable chlamydiae and depended on p44/42 mitogen-activated protein kinase activity but not on the p38 mitogen-activated protein kinase pathway. Postinfectious Egr-1 mRNA up-regulation in arterial vessels was confirmed ex vivo in a rat aortic ring model of focal vascular chlamydial infection. An in vivo model based on the injection of C. pneumoniae-infected PBMCs into mice confirmed Egr-1 mRNA up-regulation within 24 h of endovascular infection. Arterial injury from repeated direct chlamydial infections and cell-to-cell contact with C. pneumoniae-infected PBMCs might represent a chronic focus of proliferative activity linked to the media proliferation seen in advanced atherosclerosis. Overall, chlamydial infection induces a proliferative phenotype in vascular cells via transcription factor Egr-1 activation in vitro, ex vivo, and in vivo.
Rupp
Jan
J
Institutes of Medical Microbiology and Hygiene and Physiology, University of Luebeck, 23538 Luebeck, Germany.
Hellwig-Burgel
Thomas
T
Wobbe
Viola
V
Seitzer
Ulrike
U
Brandt
Ernst
E
Maass
Matthias
M
D000818:Animals; D001483:Base Sequence; D001808:Blood Vessels / Q000473:pathology*; D002455:Cell Division; D002460:Cell Line; D002690:Chlamydia Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D010641:Phenotype; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism*
D015342:DNA Probes; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D014157:Transcription Factors
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