Chlamydia pneumoniae alters mildly oxidized low-density lipoprotein-induced cell death in human endothelial cells, leading to necrosis rather than apoptosis.
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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ABSTRACT: Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development.International Journal of Molecular Sciences 01/2013; 14(7):15105-20. · 2.46 Impact Factor
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ABSTRACT: Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia (19 weeks of age) and serial sections were processed for the detection of EC apoptosis, histology, and transmission electron microscopy (TEM) studies. There was a significantly higher number of TUNEL-positive ECs in infected compared to noninfected groups [0.2942 % (interquartile ranges (IR), 0.2941; n = 26) versus 0 % (IR, 0; n = 12), p < 0.01]. Caspase-3 staining was negative. Cholesterol diet together with infections induced widening of the subendothelial space and appearance of increased numbers of foam cells. TEM revealed degenerative changes in cytoplasmic organelles and signs of EC necrosis. In conclusion, infection leads to an increase in coronary EC death and seems to exacerbate cholesterol-induced intimal thickening and foam cell accumulation.Journal of Cardiovascular Translational Research 04/2013; · 3.06 Impact Factor
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ABSTRACT: Koelreuteria formosana ethanol extract (KFEE) is obtained from natural plants that are endemic in Taiwan. A study showed that KFEE has antioxidant activity in DPPH assay. In the current study, the antioxidative activity of KFEE, which contains polyphenols including gallic acid and caffeic acid, was evaluated. The manner by which KFEE protects human umbilical vein endothelial cells (HUVECs) from oxidised LDL (oxLDL)-mediated dysfunction in vitro was investigated as well. The results indicate that the antioxidative activity of KFEE is defined by the relative electrophoretic mobility of oxLDL, the fragmentation of ApoB, conjugated diene production, and malondialdehyde production through Cu(2+)-mediated oxidation of LDL. KFEE also inhibited ROS generation as well as the subsequent mitochondrial membrane potential collapse, chromosome condensation, cytochrome C release, and caspase-3 activation induced by oxLDL in HUVECs. Our results also indicate that KFEE may protect LDL oxidation and prevent oxLDL-induced cellular dysfunction in HUVECs.Food Chemistry 03/2014; 146:299-307. · 3.33 Impact Factor