Okura Y, Brink M, Itabe H, Scheidegger K J, Kalangos A, Delafontaine P
Division of Cardiology, University Hospital of Geneva, Switzerland.
Circulation. 2000 Nov 28;102(22):2680-6. doi: 10.1161/01.cir.102.22.2680.
Cytotoxic oxidized LDL (oxLDL) has been shown to promote apoptosis in cultured vascular smooth muscle cells (VSMCs). We investigated the localization of oxLDL and its association with apoptosis and the expression of apoptosis-related proteins in early and advanced atherosclerotic lesions.
Atherosclerotic plaques (n=23) from patients undergoing aortic, carotid, or femoral arterial surgery were studied. In early lesions, oxLDL was located predominantly in the superficial intima and in the media just beneath the internal elastic lamina. Medial VSMCs staining positive for oxLDL showed expression of BAX, a proapoptotic protein of the BCL-2 family. Apoptosis, as detected by DNA in situ terminal deoxynucleotidyl transferase end-labeling (TUNEL), was not present in these early lesions. In advanced plaques, areas of the intima positive for oxLDL showed lower alpha-smooth muscle actin immunoreactivity (P<0.01) and higher BAX immunoreactivity (P<0.05). Furthermore, these areas showed an increased number of apoptotic VSMCs (P<0.01). Western blot analysis revealed that oxLDL increases BAX expression in cultured human coronary VSMCs.
We conclude that in early atherosclerotic lesions, oxLDL-positive VSMCs express BAX, which increases the susceptibility of these cells to undergo apoptosis. This could be important in our understanding of the transition of early lesions into advanced atherosclerotic plaques, which are characterized by regions of cell death. In advanced plaques, oxLDL-positive areas of the intima show higher BAX immunoreactivity and TUNEL-positive VSMCs, and this may contribute to plaque instability and rupture.
细胞毒性氧化型低密度脂蛋白（oxLDL）已被证明可促进培养的血管平滑肌细胞（VSMC）凋亡。我们研究了oxLDL在早期和晚期动脉粥样硬化病变中的定位及其与凋亡的关系以及凋亡相关蛋白的表达。
对接受主动脉、颈动脉或股动脉手术患者的动脉粥样硬化斑块（n = 23）进行了研究。在早期病变中，oxLDL主要位于内膜浅层以及内弹力膜下方的中膜。中膜中oxLDL染色阳性的VSMC显示出BCL-2家族促凋亡蛋白BAX的表达。通过DNA原位末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）检测，这些早期病变中不存在凋亡现象。在晚期斑块中，oxLDL阳性的内膜区域显示出较低的α-平滑肌肌动蛋白免疫反应性（P < 0.01）和较高的BAX免疫反应性（P < 0.05）。此外，这些区域显示凋亡的VSMC数量增加（P < 0.01）。蛋白质印迹分析显示，oxLDL可增加培养的人冠状动脉VSMC中BAX的表达。
我们得出结论，在早期动脉粥样硬化病变中，oxLDL阳性的VSMC表达BAX，这增加了这些细胞发生凋亡的易感性。这对于我们理解早期病变向以细胞死亡区域为特征的晚期动脉粥样硬化斑块的转变可能很重要。在晚期斑块中，内膜oxLDL阳性区域显示出较高的BAX免疫反应性和TUNEL阳性的VSMC，这可能导致斑块不稳定和破裂。
