Apoptosis of vascular smooth muscle cells induced by cholesterol and its oxides in vitro and in vivo

The ability of cholesterol and its oxides to induce apoptosis in vascular s mooth muscle cells in tissue culture and in a rabbit model of atheroscleros is was evaluated. Apoptosis was detected using DNA laddering and in situ en d-labelling of fragmented DNA. Cholesterol oxides, but not cholesterol, wer e found to inhibit proliferation and induce apoptosis of vascular smooth mu scle cells in tissue culture. 7-ketocholesterol was found to be the most po tent inhibitor of proliferation, while 25-hydroxycholesterol was found to b e the most potent inducer of apoptosis. These data suggest that the inhibit ion of proliferation and the induction of apoptosis by cholesterol oxides w ithin vascular smooth muscle cells use different pathways, suggesting a dif ferential role for these cholesterol oxides within the arterial wall. Chole sterol feeding after balloon injury in a rabbit model of atherosclerosis is known to result in the accumulation of cholesterol oxides. However, we fou nd that cholesterol feeding had no effect on the level of apoptosis in the rabbit aortic wall after balloon injury, suggesting that the major factor d etermining apoptosis in our model was the balloon injury. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.