Niculescu Florin, Niculescu Teodora, Rus Horea
Department of Pathology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Exp Mol Pathol. 2004 Feb;76(1):17-23. doi: 10.1016/j.yexmp.2003.10.002.
Apoptosis plays an important role in atherosclerosis. The factors regulating this process are not well defined. We examined the relation of apoptotic cells with the terminal complement complex C5b-9 in human atherosclerotic lesions. The extent of apoptosis was determined using TdT dUTP nick-end labeling (TUNEL) and immunohistochemistry of apoptosis regulators caspase-3, caspase-9, Bax, and Bcl-2. C5b-9 was localized by immunohistochemistry and immunoelectron microscopy. The apoptotic index was higher in fibrous plaques when compared with intimal fatty streaks and intimal thickenings. Bax expression was present in TUNEL+ apoptotic cells, and Bcl-2 was rarely present in the atherosclerotic wall. Active caspase 9 and caspase 3 deposits were present in the same areas, suggesting an involvement of the mitochondrial pathway. C5b-9 deposits colocalized with TUNEL+ cells, and the percent of double-positive cells was 2% in fatty streaks, 12% in intimal thickenings, and 35% in fibrous plaques. Colocalization of apoptotic cells with C5b-9 was also confirmed by immunoelectron microscopy. In conclusion, some apoptotic cells carry C5b-9 deposits, suggesting that complement might be activated by apoptotic cells and involved in the promotion of apoptosis, contributing to the progression of atherosclerotic lesions.
细胞凋亡在动脉粥样硬化中发挥着重要作用。调节这一过程的因素尚未完全明确。我们研究了人类动脉粥样硬化病变中凋亡细胞与终末补体复合物C5b-9的关系。使用TdT dUTP缺口末端标记法（TUNEL）以及凋亡调节因子半胱天冬酶-3、半胱天冬酶-9、Bax和Bcl-2的免疫组织化学方法来确定凋亡程度。通过免疫组织化学和免疫电子显微镜对C5b-9进行定位。与内膜脂肪条纹和内膜增厚相比，纤维斑块中的凋亡指数更高。Bax表达存在于TUNEL阳性的凋亡细胞中，而Bcl-2在动脉粥样硬化壁中很少出现。活性半胱天冬酶9和半胱天冬酶3沉积物存在于相同区域，提示线粒体途径参与其中。C5b-9沉积物与TUNEL阳性细胞共定位，脂肪条纹中双阳性细胞的百分比为2%，内膜增厚中为12%，纤维斑块中为35%。免疫电子显微镜也证实了凋亡细胞与C5b-9的共定位。总之，一些凋亡细胞带有C5b-9沉积物，这表明补体可能被凋亡细胞激活并参与促进细胞凋亡，从而导致动脉粥样硬化病变的进展。
