Oxidized LDL Induces Apoptosis in Cultured Smooth Muscle Cells: A Possible Role for 7-Ketocholesterol

• Published in: Biochemical and biophysical research communications Vol. 223; no. 2; pp. 413 - 418
• Main Authors: Nishio, Eisuke, Arimura, Shinya, Watanabe, Yasuhiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.06.1996
• Subjects: Animals; Aorta, Thoracic; Apoptosis - drug effects; Cells, Cultured; Cholesterol - pharmacology; DNA - analysis; DNA - drug effects; Dose-Response Relationship, Drug; Humans; Ketocholesterols - pharmacology; Ketocholesterols - physiology; Kinetics; Lipoproteins, LDL - blood; Lipoproteins, LDL - isolation & purification; Lipoproteins, LDL - pharmacology; Lysophosphatidylcholines - pharmacology; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Oxidation-Reduction; Rabbits
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1996.0907

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.