Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting enzyme.
Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting enzyme.
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发表时间：
1995-08
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通讯作者：
Y. Geng;P. Libby
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作者：
Y. Geng;P. Libby
本研究旨在寻找人类动脉粥样硬化冠状动脉和颈动脉中细胞凋亡（程序性细胞死亡的一种形式）的证据。凋亡细胞的标志物包括原位末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL），基因组DNA电泳和形态学分析。内膜病变包含更多的TUNEL+细胞（34 +/-6%，n = 8）比非动脉粥样硬化动脉内膜（8 +/-3%，n = 5，P < 0.05）。病变动脉的图尼卡中膜具有与正常血管中相似的TUNEL+细胞百分比（5 +/- 1%）（3 +/-1%，N.S.）。在12个动脉粥样硬化斑块的提取物中可观察到寡核小体DNA片段，但在5个非动脉粥样硬化血管中均未观察到。两个平滑肌细胞（SMC）和巨噬细胞，两种主要的细胞类型在动脉粥样硬化内膜，孔凋亡的标志物，但不同的模式，所确定的双重组织化学标记的细胞类型和TUNEL。TUNEL+ SMC主要位于粥样硬化的纤维化部分，而TUNEL+巨噬细胞聚集在病变的富脂核心附近或内部。逆转录聚合酶链反应显示，动脉粥样硬化病变表达编码白细胞介素-1 β转换酶（ICE）的mRNA，ICE是一种哺乳动物细胞死亡基因。免疫组化显示ICE主要定位于TUNEL+ SMC和巨噬细胞区域。TUNEL-细胞显示很少或没有免疫反应ICE。这些数据表明细胞凋亡在动脉粥样硬化形成期间调节细胞积聚中的作用，并表明ICE参与了复杂动脉粥样硬化纤维区域的SMC死亡以及病变富含脂质核心的巨噬细胞死亡。纤维帽内血管细胞的凋亡可能阻碍该区域基质的维持或修复，影响斑块的稳定性。
This study sought evidence for apoptosis, a form of programmed cell death, in human atheromatous coronary and carotid arteries. Markers for apoptotic cells included in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), genomic DNA electrophoresis, and morphological analysis. Intimal lesions contained more TUNEL+ cells (34 +/- 6%, n = 8) than non-atherosclerotic arterial intima (8 +/- 3%, n = 5, P < 0.05). The tunica media of the diseased arteries had a percentage of TUNEL+ cells (5 +/- 1%) similar to that in the normal vessels (3 +/- 1%, N.S.). Oligonucleosomal DNA fragments were visualized in extracts from 12 atheromatous plaques but in none of 5 non-atherosclerotic vessels. Both smooth muscle cells (SMC) and macrophages, two major cell types in the atherosclerotic intima, bore markers of apoptosis, but with different patterns, as determined by double histochemical labeling for cell types and TUNEL. The TUNEL+ SMC localized mainly in the fibrotic portion of the atheroma, whereas TUNEL+ macrophages clustered near or within the lipid-rich core of the lesion. Atheromatous lesions expressed mRNA encoding interleukin-1 beta-converting enzyme (ICE), a mammalian cell death gene, as demonstrated by reverse transcriptase polymerase chain reaction. Immunohistochemistry revealed that ICE localized in regions of TUNEL+ SMC and macrophages. TUNEL- cells showed little or no immunoreactive ICE. These data point to a role for apoptosis in regulation of cell accumulation during atherogenesis and suggest involvement of ICE in SMC death in fibrous regions of complex atheroma, and in macrophage death in the lipid-rich core of the lesion. Apoptosis of vascular cells in fibrous cap may impede maintenance or repair of the matrix in this region and affect stability of the plaques.