在动脉样硬化中蛋白质分解活性的体内成像
Jiqiu Chen1, Ching-Hsuan Tung, Umar Mahmood
1Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Circulation
|June 12, 2002
概括
与炎症相关的酶Cathepsin B在脆弱的动脉样硬化斑块中升高. 新型成像信标可以在体内检测甲素B活性,有助于识别高风险斑块.
科学领域:
- 心血管研究研究心血管研究
- 生物标志物发现发现
- 分子成像学分子成像学
背景情况:
- 血管炎症是动脉样硬化斑块破裂的关键因素,是心血管事件的主要原因.
- 蛋白质溶解是由像甲素B这样的酶驱动的,被假定会导致斑块不稳定.
- 甲素B作为一种模型酶,用于研究蛋白质分解在动脉样硬化中的作用.
研究的目的:
- 为了研究 cathepsin B 在动脉样硬化斑块脆弱性中的作用.
- 开发和验证新型成像剂,用于检测cathepsin B活体中的活性.
- 评估使用先进的断层扫描系统在动脉样硬化病变中成像cathepsin B活性的可行性.
主要方法:
- 利用西方类型的饮食养的apoE和apoE/内皮NO合成双重淘汰的小鼠作为动脉样.
- 采用了静脉注射式甲素B成像信标和近红外断层成像系统.
- 进行了西部涂抹和免疫组织化学,以评估甲素B水平和局部化.
主要成果:
- 与正常的大动脉或静音病变相比,在炎症性动脉样性病变中,甲素B的表达显著上调.
- 甲素B成像信标在活跃的动脉样硬化病变中表现出高活性,与甲素B免疫活性共定位.
- 在体内断层成像成功地可视化了整个动物动脉样硬化病变中的甲素B活性.
结论:
- 甲素B,以及潜在的其他蛋白酶,可以作为生物标记物来识别易受动脉样硬化斑块的脆弱性.
- 开发的体内断层成像和以导管为基础的光学传感方法显示出对脆弱斑块中蛋白酶的查和分子分析有前途.
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