Article

Chlamydia pneumoniae alters mildly oxidized low-density lipoprotein-induced cell death in human endothelial cells, leading to necrosis rather than apoptosis.

INSERM U466, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil and Universite Paul Sabatier, Toulouse, France.
The Journal of Infectious Diseases (impact factor: 6.41). 02/2006; 193(1):136-45. DOI:10.1086/498617 pp.136-45
Source: PubMed

ABSTRACT 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.
The in vitro effect of C. pneumoniae infection on apoptosis induced by mildly oxidized LDLs (moxLDLs) in human endothelial cells was studied.
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.
C. pneumoniae infection enhances the inflammatory action of oxLDLs in the vascular wall, leading to cell necrosis rather than apoptosis.

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Keywords

apoptosis induced
 
apoptotic features
 
C. pneumoniae
 
C. pneumoniae infection
 
cell death
 
cell death induced
 
cell necrosis
 
cell survival
 
cytochrome c release
 
human endothelial cells
 
induce apoptosis
 
Infection inhibited apoptosis
 
lactate dehydrogenase release
 
low-molecular-mass PARP fragments
 
mildly oxidized LDLs
 
necrosis-like cell death
 
necrotic cellular morphological characteristics
 
Oxidized low-density lipoproteins
 
strong increase
 
vascular cells