Chlamydia pneumoniae alters mildly oxidized low-density lipoprotein-induced cell death in human endothelial cells, leading to necrosis rather than apoptosis.
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.
Nazzal
Dani
D
INSERM U466, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil and Universite Paul Sabatier, Toulouse, France.
Cantero
Anne-Valerie
AV
Therville
Nicole
N
Segui
Bruno
B
Negre-Salvayre
Anne
A
Thomsen
Mogens
M
Benoist
Herve
H
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
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein