基于aptamer的蛋白质分析揭示了心血管疾病中的新生物标志物和途径
Debby Ngo1, Sumita Sinha1, Dongxiao Shen1
1From Division of Pulmonary and Critical Care Medicine, Department of Medicine (D.N.) and the Cardiovascular Research Center (D.N., S.S., D.S., M.J.K., X.S., M.D.B., J.F.O., L.A.F., R.E.G.), Massachusetts General Hospital, Harvard Medical School, Boston; Broad Institute of MIT and Harvard, Cambridge, MA (E.W.K., H.K., S.A.C., R.E.G.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.D.B., M.S.S.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (M.A.F., M.S.S., R.E.G.); Preventive Medicine Section, Department of Medicine, Boston University School of Medicine, MA (R.S.V.); Department of Biostatistics, Boston University School of Public Health, MA (M.G.L.); The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (M.G.L.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA (R.E.G.).
一个基于aptamer的蛋白质组平台发现了心肌损伤的新生物标志物,检测了心肌梗塞后的200多种蛋白质变化. 这项技术可以对大量人群进行高通量蛋白质组分析.
科学领域:
- 蛋白质组学
- 生物标志物发现
- 心血管研究
背景情况:
- 单链DNA胺为蛋白质结合提供了高的特异性和亲和力.
- 基于aptamer的技术提供了传统蛋白质组方法的替代方案,解决了样本吞吐量低等局限性.
研究的目的:
- 通过基于aptamer的蛋白质平台识别心肌损伤的早期生物标志物.
- 在心肌梗塞和大量人群的临床模型中评估平台的性能.
主要方法:
- 在计划性心肌梗塞 (PMI) 模型中应用了测量1129种蛋白质的基于aptamer的蛋白质基平台.
- 在PMI前后 (10分钟和60分钟) 采集血液样本并分析蛋白质变化.
- 在独立的PMI队列中验证的结果和Framingham风险评分组件的评估关联.
主要成果:
- 在PMI后的周围血液中发现了217种显著变化的蛋白质,其中79种在独立的队列中得到验证.
- 发现了新的心肌损伤生物标志物,包括Dickkopf相关的蛋白4和crypto.
- 在自发性心肌梗塞患者中发现了23个验证的蛋白质升高和156个显著的蛋白质关联与Framingham风险评分.
结论:
- 基于aptamer的蛋白质组学工具可以对1000多种低丰度分析物进行高灵敏度和精度的分析.
- 这种技术既适用于详细的扰动研究,也适用于大规模的人类队列分析.
- 该平台有助于发现心肌损伤和心血管风险评估的新生物标志物.
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