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.