Oxidized LDL induces apoptosis in cultured smooth muscle cells: a possible role for 7-ketocholesterol.
In the multifunctional pathogens of atherosclerosis, oxidatively modified low density lipoprotein (LDL) plays a central role in atherogenesis. We searched to find out whether oxidized LDL (ox-LDL) could induce apoptosis in smooth muscle cells (SMCs). The induction of apoptosis was demonstrated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling and DNA fragmentation. Ox-LDL induced apoptosis in a concentration dependent manner in the cells. The structural and biological changes in ox-LDL may be attributed to lysophosphatidylcholine (lyso-PC) accumulation and lipid peroxidation. To determine whether lyso-PC or lipid peroxide is responsible for the biological effect of ox-LDL, we incubated SMCs with lyso-PC or 7-ketocholesterol. Lyso-PC did not induce apoptosis, but 7-ketocholesterol did induce apoptosis. We conclude that ox-LDL induces apoptosis in SMCs and that this apoptosis contributes to lipid peroxidation. This mechanism may be important in determining the course of atherogenesis.
Nishio
E
E
Department of Pharmacology, National Defense Medical College, Saitama, Japan.
Arimura
S
S
Watanabe
Y
Y
D000818:Animals; D001013:Aorta, Thoracic; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007653:Ketocholesterols / Q000494:pharmacology* / Q000502:physiology; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010084:Oxidation-Reduction; D011817:Rabbits
D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D004247:DNA; D002784:Cholesterol; C003001:7-ketocholesterol