title: Chlamydia pneumoniae alters mildly oxidized low-density lipoprotein-induced cell death in human endothelial cells, leading to necrosis rather than apoptosis.
abstract: BACKGROUND
  Atherosclerosis is characterized by oxidative stress that induces lipid and protein oxidation in the vascular wall. Oxidized low-density lipoproteins (oxLDLs) are present in lesions, and one of their actions is to induce apoptosis or necrosis in vascular cells. A role for Chlamydia pneumoniae in atherosclerosis has been proposed, but the mechanisms involved remain largely unknown.
  
  
  METHODS
  The in vitro effect of C. pneumoniae infection on apoptosis induced by mildly oxidized LDLs (moxLDLs) in human endothelial cells was studied.
  
  
  RESULTS
  Infection inhibited apoptosis, as was demonstrated by a decrease in such apoptotic features as cytochrome c release, caspase activity, 89-kilodalton poly(ADP-ribose) polymerase (PARP) fragment formation, nuclear condensation and fragmentation, and DNA fragmentation. However, the inhibition of apoptosis did not favor cell survival, because infection promoted cell death with necrotic features, as was illustrated by an increase in lactate dehydrogenase release, an enhancement of necrotic cellular morphological characteristics, and generation of low-molecular-mass PARP fragments. The increase in occurrence of necrosis-like cell death was correlated with a strong increase in intracellular reactive oxygen species (ROS) concentration. Vitamin E inhibited ROS production and promoted cell survival, underscoring the involvement of ROS in cell death induced by the combination of C. pneumoniae and moxLDLs.
  
  
  CONCLUSIONS
  C. pneumoniae infection enhances the inflammatory action of oxLDLs in the vascular wall, leading to cell necrosis rather than apoptosis.
authors.affiliation: INSERM U466, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil and Universite Paul Sabatier, Toulouse, France.
authors.forename: Dani
authors.initials: D
authors.lastname: Nazzal
authors.forename: Anne-Valerie
authors.initials: AV
authors.lastname: Cantero
authors.forename: Nicole
authors.initials: N
authors.lastname: Therville
authors.forename: Bruno
authors.initials: B
authors.lastname: Segui
authors.forename: Anne
authors.initials: A
authors.lastname: Negre-Salvayre
authors.forename: Mogens
authors.initials: M
authors.lastname: Thomsen
authors.forename: Herve
authors.initials: H
authors.lastname: Benoist
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D042783:Endothelial Cells / Q000382:microbiology* / Q000473:pathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D009336:Necrosis; D010084:Oxidation-Reduction
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein