title: Oxidized LDL promotes the mitogenic actions of Chlamydia pneumoniae in vascular smooth muscle cells.
abstract: OBJECTIVE
  The atherogenic actions of Chlamydia pneumoniae (C. pneumoniae), a common respiratory pathogen, are dependent upon a high-cholesterol environment in vivo. It is possible that oxidized low-density lipoprotein (oxLDL) is responsible for promoting the atherogenic effects of C. pneumoniae through a stimulation of cell proliferation. This study determined whether oxLDL can enhance the mitogenic action of C. pneumoniae in vascular smooth muscle cells (VSMCs) and the involvement of mitogen-activated protein kinase (MAPK) pathways and heat shock protein 60 (HSP60) in these mechanisms.
  
  
  RESULTS
  Primary rabbit VSMCs were treated with live C. pneumoniae, heat-inactivated C. pneumoniae or infection medium, and subsequently incubated for up to 48 h in the presence or absence of oxLDL. Chlamydia pneumoniae infection alone stimulated cell proliferation and the addition of oxLDL significantly amplified this proliferative effect. This proliferation was accompanied by extracellular signal-regulated kinase-1 and -2 (ERK1/2) activation and an up-regulation of HSP60 expression. Changes in proliferation and HSP60 expression were attenuated by the inhibition of ERK1/2.
  
  
  CONCLUSIONS
  These results indicate a novel role for oxLDL in promoting the mitogenic actions of C. pneumoniae in the vasculature. ERK1/2 is an important factor in the stress-mediated response and HSP60 up-regulation in VSMC. These data provide mechanistic evidence that C. pneumoniae may stimulate atherogenesis.
authors.affiliation: Institute of Cardiovascular Sciences, St Boniface Hospital Research Centre, 351 Tache Ave., Winnipeg, Manitoba,  Canada R2H 2A6.
authors.forename: Mirna N
authors.initials: MN
authors.lastname: Chahine
authors.forename: Justin
authors.initials: J
authors.lastname: Deniset
authors.forename: Elena
authors.initials: E
authors.lastname: Dibrov
authors.forename: Satoru
authors.initials: S
authors.lastname: Hirono
authors.forename: David P
authors.initials: DP
authors.lastname: Blackwood
authors.forename: Jose Alejandro
authors.initials: JA
authors.lastname: Austria
authors.forename: Grant N
authors.initials: GN
authors.lastname: Pierce
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D004789:Enzyme Activation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D018834:Chaperonin 60; D008077:Lipoproteins, LDL; D047428:Protein Kinase Inhibitors; C099252:oxidized low density lipoprotein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3