Regulatory effects of aggregated LDL on apoptosis during foam cell formation of human peripheral blood monocytes.
In order to investigate the mechanisms how modified lipoproteins enhance foam cell formation, we cultured peripheral blood monocytes with various stimulants and examined the effects of aggregated low-density lipoprotein (agLDL) on cell viability and lipid metabolism. AgLDL could completely inhibit phorbol ester-induced apoptosis, which was accompanied by intracellular cholesterol accumulation. Suppression of apoptosis-promoting proteases, ICE and CPP32, was observed in agLDL-treated cells. This indicates that agLDL accelerates foam cell formation through inhibition of apoptosis and enhancement of lipid accumulation in activated monocytes. By contrast, apoptosis was enhanced when monocytes were cultured with agLDL and M-CSF. Intracellular cholesterol accumulation was not significant in M-CSF treated cells. This suggests that M-CSF may act anti-atherogenic through apoptotic elimination of lipid-baring macrophages and enhanced lipid turnover. Our observation supports the novel hypothesis that regulation of apoptosis may play an important role in the development of atherosclerosis.
Kubo
N
N
Clinical Laboratories, Omiya Medical Center, Jichi Medical School, Saitama, Japan.
Kikuchi
J
J
Furukawa
Y
Y
Sakai
T
T
Ohta
H
H
Iwase
S
S
Yamada
H
H
Sakurabayashi
I
I
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002788:Cholesterol Esters / Q000235:genetics; D005487:Foam Cells / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002787:Sterol Esterase / Q000235:genetics; D002785:Sterol O-Acyltransferase / Q000235:genetics
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase