Fas is expressed in human atherosclerotic intima and promotes apoptosis of cytokine-primed human vascular smooth muscle cells
Fas is expressed in human atherosclerotic intima and promotes apoptosis of cytokine-primed human vascular smooth muscle cells
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DOI：
10.1161/01.atv.17.10.2200
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发表时间：
1997-10-01
影响因子：
8.7
通讯作者：
Libby, P
中科院分区：
文献类型：
--
作者：
Geng, YJ;Henderson, LE;Libby, P
膜蛋白Fas/Apo-1/CD95信号转导活化T淋巴细胞的程序性细胞死亡或凋亡。在含有免疫细胞的晚期动脉粥样硬化斑块中，血管平滑肌细胞(SMCs)带有细胞程序性死亡或凋亡的标志，如巨噬细胞和T淋巴细胞。这项研究验证了假设，即Fas死亡信号通路有助于动脉粥样硬化形成过程中暴露于这些免疫细胞产生的促炎细胞因子的SMC的凋亡。所有检查的动脉粥样硬化斑块(n=14)均含有免疫反应Fas。大多数Fas(+)的SMC定位于斑块内膜，而中层SMC表达Fas抗原的程度较低。DNA片段(TUNEL)和Fas的双重染色或细胞识别标记Fas与TUNEL+SMC共存于含有CD3(+)T细胞和CD68(+)巨噬细胞的区域，提示Fas在动脉粥样硬化形成过程中活化的T细胞诱导SMC凋亡中起作用。在培养中，干扰素-γ、肿瘤坏死因子-α和白介素1-β刺激增加了SMC中Fas的表达。用激活的抗Fas抗体孵育可引起细胞因子启动的SMC的凋亡，但不能引起未经处理的SMC的凋亡，TUNEL和寡核小体DNA片段的电泳法证明。这些数据表明，Fas死亡信号通路的激活有助于在动脉粥样硬化形成过程中诱导SMC凋亡，并提供了一种免疫细胞及其细胞因子促进与血管重构和斑块破裂相关的细胞死亡过程的机制。
The membrane protein Fas/Apo-1/CD95 signals programmed cell death or apoptosis in activated T lymphocytes. Vascular smooth muscle cells (SMCs) bear markers of programmed cell death or apoptosis in advanced atherosclerotic plaques that contain immune cells eg, macrophages and T lymphocytes. This study tested the hypothesis that the Fas death-signaling pathway contributes to apoptosis of SMCs exposed to proinflammatory cytokines produced by these immune cells during atherogenesis. All atherosclerotic plaques examined (n=14) contained immunoreactive Fas. The majority of the Fas(+) SMCs localized in the intima of the plaques, whereas the medial SMCs expressed Fas antigen less prominently. Double staining for DNA fragments (TUNEL) and Fas or cell identification markers colocalized Fas with TUNEL+ SMCs in the areas that contained CD3(+) T cells and CD68(+) macrophages, suggesting a role for Fas in the induction of SMC apoptosis by activated T cells during atherogenesis. In culture, stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta increased expression of Fas in SMCs. Incubation with an activating anti-Fas antibody triggered apoptosis of the cytokine-primed but not the untreated SMCs, as demonstrated by TUNEL and electrophoresis of oligonucleosomal DNA fragments. These data suggest that activation of the Fas death-signaling pathway contributes to the induction of SMC apoptosis during atherogenesis and furnish a mechanism whereby immune cells and their cytokines promote this cell death process related to vascular remodeling and plaque rupture.