Yin J, Chaufour X, McLachlan C, McGuire M, White G, King N, Hambly B
Department of Pathology, University of Sydney, Sydney, Australia.
Atherosclerosis. 2000 Feb;148(2):365-74. doi: 10.1016/s0021-9150(99)00286-5.
The ability of cholesterol and its oxides to induce apoptosis in vascular smooth muscle cells in tissue culture and in a rabbit model of atherosclerosis was evaluated. Apoptosis was detected using DNA laddering and in situ end-labelling of fragmented DNA. Cholesterol oxides, but not cholesterol, were found to inhibit proliferation and induce apoptosis of vascular smooth muscle cells in tissue culture. 7-ketocholesterol was found to be the most potent inhibitor of proliferation, while 25-hydroxycholesterol was found to be the most potent inducer of apoptosis. These data suggest that the inhibition of proliferation and the induction of apoptosis by cholesterol oxides within vascular smooth muscle cells use different pathways, suggesting a differential role for these cholesterol oxides within the arterial wall. Cholesterol feeding after balloon injury in a rabbit model of atherosclerosis is known to result in the accumulation of cholesterol oxides. However, we found that cholesterol feeding had no effect on the level of apoptosis in the rabbit aortic wall after balloon injury, suggesting that the major factor determining apoptosis in our model was the balloon injury.
评估了胆固醇及其氧化物在组织培养和兔动脉粥样硬化模型中诱导血管平滑肌细胞凋亡的能力。使用DNA梯状条带分析和DNA片段原位末端标记法检测凋亡。发现胆固醇氧化物而非胆固醇可抑制组织培养中血管平滑肌细胞的增殖并诱导其凋亡。7-酮胆固醇是最有效的增殖抑制剂，而25-羟胆固醇是最有效的凋亡诱导剂。这些数据表明，血管平滑肌细胞内胆固醇氧化物对增殖的抑制和对凋亡的诱导作用通过不同途径，提示这些胆固醇氧化物在动脉壁中具有不同作用。已知在兔动脉粥样硬化模型中，球囊损伤后喂食胆固醇会导致胆固醇氧化物的积累。然而，我们发现喂食胆固醇对球囊损伤后兔主动脉壁的凋亡水平没有影响，这表明在我们的模型中决定凋亡的主要因素是球囊损伤。
