Evidence for the rapid onset of apoptosis in medial smooth muscle cells after balloon injury.

Evidence for the rapid onset of apoptosis in medial smooth muscle cells after balloon injury.
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球囊损伤后内侧平滑肌细胞凋亡快速发生的证据。

DOI:
10.1161/01.cir.95.4.981
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发表时间:
1997
期刊:
影响因子:
37.8
通讯作者:
Walsh,K
Walsh,K
中科院分区:
医学1区
文献类型:
--
作者:
Perlman,H;Maillard,L;Krasinski,K;Walsh,K

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背景在人动脉粥样硬化斑块切除术和动脉内膜切除术标本中,以及在球囊损伤的大鼠颈动脉损伤后 7 至 30 天内,新生内膜平滑肌细胞 (SMC) 均报告有血管肌细胞凋亡细胞死亡。然而,球囊损伤对内侧 SMC 活力的直接影响尚未得到检验。方法和结果在球囊损伤时 (T=0) 以及损伤后 0.5、1、2 和 4 小时采集大鼠颈动脉。未损伤的血管或损伤时收获的血管(T=0)没有显示出细胞凋亡的证据。然而,早在损伤后 30 分钟,通过 TdT 介导的 dUTP 缺口末端标记 (TUNEL) 分析和浓缩染色质的出现,70% 的内侧 SMC 出现凋亡。在损伤后 1 小时和 2 小时也观察到高频率的 TUNEL 阳性细胞,但在 4 小时则没有观察到。透射电镜观察损伤切片中可见大量细胞具有凋亡的形态特征。在培养基的最管腔层中检测到 bcl-X 表达显着下降。为了在第二个动物模型中证实这些发现,在球囊血管成形术后对兔髂外动脉进行了分析。兔动脉损伤后 30 分钟和 4 小时出现明显的细胞凋亡。 结论 早在球囊损伤后 30 分钟,TUNEL 染色、染色质浓缩和电镜形态特征显示,心肌细胞就出现高频细胞凋亡。细胞凋亡的诱导与 bcl-X 表达的显着下调同时发生。
BackgroundVascular myocyte apoptotic cell death has been reported in human atherectomy and endarterectomy specimens and for neointimal smooth muscle cells (SMCs) in balloon-injured rat carotid arteries between 7 and 30 days after injury. However, the immediate effect of balloon injury on medial SMC viability has not been examined.Methods and ResultsRat carotid arteries were harvested at the time of balloon injury (T=0) and at 0.5, 1, 2, and 4 hours after injury. Uninjured vessels or vessels harvested at the time of injury (T=0) did not display evidence of apoptosis. However, as early as 30 minutes after injury, 70% of medial SMCs appeared apoptotic by TdT-mediated dUTP nick end labeling (TUNEL) analysis and by the appearance of condensed chromatin. High frequencies of TUNEL-positive cells were also observed at 1 and 2 hours after injury but not at 4 hours. Transmission electron microscopy revealed many cells with morphological characteristics of apoptosis in the injured sections. A marked decrease in bcl-X expression was detected in the most luminal layers of the media. To corroborate these findings in a second animal model, rabbit external iliac arteries were analyzed after balloon angioplasty. Apoptotic cell death was evident in rabbit arteries at 30 minutes and at 4 hours after injury.ConclusionsAs early as 30 minutes after balloon injury, myocytes appear to undergo apoptotic cell death at a high frequency as shown by TUNEL staining, chromatin condensation, and the appearance of morphological features in electron micrographs. The induction of apoptosis coincides with a marked downregulation of bcl-X expression.