AIMS: 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. METHODS AND 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. CONCLUSION: 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.
AIMS: 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. METHODS AND 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. CONCLUSION: 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: Pamela R Hall; Bradley O Elmore; Cynthia H Spang; Susan M Alexander; Brett C Manifold-Wheeler; Moriah J Castleman; Seth M Daly; M Michal Peterson; Erin K Sully; Jon K Femling; Michael Otto; Alexander R Horswill; Graham S Timmins; Hattie D Gresham Journal: PLoS Pathog Date: 2013-02-14 Impact factor: 6.823