在动脉样硬化斑块中增加了内质网膜应激,与急性冠状动脉综合征相关
Masafumi Myoishi1, Hiroyuki Hao, Tetsuo Minamino
1Department of Cardiovascular Medicine, National Cardiovascular Center, Suita, Osaka 565-8565, Japan.
Circulation
|August 22, 2007
概括
在不稳定的冠状动脉斑块中,内质网膜 (ER) 应激和亡增加. 这表明ER压力诱导的细胞死亡有助于斑块脆弱性,这是心脏病发作的一个关键因素.
科学领域:
- 心血管生物学 心血管生物学
- 细胞应激反应的应激反应
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 细胞内膜网膜 (ER) 的压力会触发伴侣细胞的产生,但长时间的压力会导致亡.
- 亡在动脉样硬化斑块的进展和破裂中至关重要.
- 在不稳定的冠状动脉斑块破裂中ER压力和亡的作用尚未完全理解.
研究的目的:
- 调查ER压力,亡和冠状动脉样硬化斑块的脆弱性之间的联系.
主要方法:
- 来自患者的冠状动脉和心脏切除样本的分析.
- 评估ER陪伴体表达,亡细胞和7 - 基托胆固醇水平.
- 在体外研究中,使用培养细胞治疗7-基托胆固醇和抗氧化剂.
- 调查CHOP依赖的信号通路和siRNA介导的淘汰.
主要成果:
- 增加ER陪伴细胞表达和亡细胞被观察到纤维状帽子的薄帽动脉瘤和破裂的斑块.
- 在不稳定的胸痛患者的样本中发现了更高的ER陪伴表达.
- 7-基托胆固醇诱导了培养细胞中的ER陪伴者和亡,抗氧化剂阻断了效果.
- 在不稳定的斑块中激活了CHOP依赖性途径,CHOP的敲除减少了ER压力诱导的细胞死亡.
结论:
- 不稳定的冠状动脉斑块表现出 endoplasmic reticulum 增加的压力.
- 平滑肌细胞和巨细胞的ER压力诱导的亡可能有助于斑块脆弱性.
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