Kockx M M, De Meyer G R, Muhring J, Jacob W, Bult H, Herman A G
Department of Pathology, A.Z. Middelheim, Antwerp, Belgium.
Circulation. 1998 Jun 16;97(23):2307-15. doi: 10.1161/01.cir.97.23.2307.
The transition of a fatty streak into an atherosclerotic plaque is characterized by the appearance of focal and diffuse regions of cell death. We have investigated the distribution of apoptotic cell death and apoptosis-related proteins in early and advanced atherosclerotic lesions.
Human atherosclerotic plaques were studied by whole-mount carotid endarterectomy specimens (n=18). This approach allowed comparison of adaptive intimal thickenings, fatty streaks, and advanced atherosclerotic plaques of the same patient. The fatty streaks differed from adaptive intimal thickenings by the presence of BAX (P<0.01), a proapoptotic protein of the BCL-2 family. Both regions were composed mainly of smooth muscle cells (SMCs), and macrophage infiltration was low and not different. Apoptosis, as detected by DNA in situ end labeling (terminal deoxynucleotidyl transferase end labeling [TUNEL] and in situ nick translation) was not present in these regions. Apoptosis of SMCs and macrophages, however, was present in advanced atherosclerotic plaques that were present mainly in the carotid sinus. A dense infiltration of macrophages (5.8+/-3% surface area) was present in these advanced atherosclerotic plaques. Cytoplasmic remnants of apoptotic SMCs, enclosed by a cage of thickened basal lamina, were TUNEL negative and remained present in the plaques as matrix vesicles.
We conclude that SMCs within human fatty streaks express BAX, which increases the susceptibility of these cells to undergo apoptosis. The localization of these susceptible SMCs in the deep layer of the fatty streaks could be important in our understanding of the transition of fatty streaks into atherosclerotic plaques, which are characterized by regions of cell death. Matrix vesicles are BAX-immunoreactive cytoplasmic remnants of fragmented SMCs that can calcify and may be considered the graves of SMCs that have died in the plaques.
脂肪条纹向动脉粥样硬化斑块的转变以细胞死亡的局灶性和弥漫性区域出现为特征。我们研究了早期和晚期动脉粥样硬化病变中凋亡细胞死亡及凋亡相关蛋白的分布。
通过全颈动脉内膜切除术标本（n = 18）研究人类动脉粥样硬化斑块。这种方法能够比较同一患者的适应性内膜增厚、脂肪条纹和晚期动脉粥样硬化斑块。脂肪条纹与适应性内膜增厚的区别在于存在BAX（P<0.01），它是BCL-2家族的促凋亡蛋白。这两个区域主要由平滑肌细胞（SMC）组成，巨噬细胞浸润较少且无差异。通过DNA原位末端标记（末端脱氧核苷酸转移酶末端标记法[TUNEL]和原位缺口平移）检测，这些区域不存在凋亡现象。然而，SMC和巨噬细胞的凋亡存在于主要位于颈动脉窦的晚期动脉粥样硬化斑块中。这些晚期动脉粥样硬化斑块中有密集的巨噬细胞浸润（表面积为5.8±3%）。凋亡SMC的细胞质残余物被增厚的基底膜包裹，TUNEL检测呈阴性，并作为基质小泡保留在斑块中。
我们得出结论，人类脂肪条纹内的SMC表达BAX，这增加了这些细胞发生凋亡的易感性。这些易感性SMC在脂肪条纹深层的定位对于我们理解脂肪条纹向以细胞死亡区域为特征的动脉粥样硬化斑块的转变可能很重要。基质小泡是破碎SMC的BAX免疫反应性细胞质残余物，可发生钙化，可被视为在斑块中死亡的SMC的“坟墓”。
