对内皮细胞S-硫的绘制突显了整体硫在血管功能中的关键作用
Sofia-Iris Bibli1,2, Jiong Hu1,2, Mario Looso2,3
1Institute for Vascular Signalling (S-I.B., J.H., J.W., M.K.D., V.R., F.D.L., B.F., S.Z., A.K., A.F.O.J., I.F.), Goethe University, Frankfurt am Main, Germany.
Circulation
|December 14, 2020
概括
与硫化相关的硫化合物 (H2Sn) 改变内皮细胞中的蛋白质,影响血管功能. 补充H2Sn改善了患者的血管反应,这表明血管疾病的治疗潜力.
科学领域:
- 生物化学
- 分子生物学
- 血管生物学
背景情况:
- 在血管内皮细胞中通过cystathionine γ lyase (CSE) 的代谢产生与硫化相关的硫化合物 (H2Sn).
- H2Sn通过氨酸S-硫化对蛋白进行生物作用.
- 这项研究旨在绘制人体内皮细胞中的S-硫.
研究的目的:
- 在人类内皮细胞中识别H2Sn (S-硫) 向的蛋白质.
- 调查S-硫化在内皮细胞功能中的作用,特别是对流动的反应.
- 探索H2Sn补充剂在血管疾病中的治疗潜力.
主要方法:
- 使用双重质谱 (LC-MS/MS) 的液体染色法用于识别S-硫化氨酸.
- 从健康与动脉硬化的人体内皮细胞的比较分析,静态与剪切应激条件,以及H2Sn供体治疗.
- 功能测定包括小鼠和人类的细胞粘附,对齐,血压和流动诱导血管扩张研究.
主要成果:
- 内皮细胞的S-硫体包含1591个蛋白质中的3446个半氨酸残留物.
- 综合素,特别是β3综合素,受到显著影响,S-硫化调节其构成和机械传导.
- 与动脉样硬化中的内皮功能障碍相关的β3整合素S-硫化受损,并通过H2Sn补充得到救助.
结论:
- 血管疾病的特征是参与流动反应的内皮蛋白质的S-硫化发生变化.
- 在人体中,短期服用H2Sn补充剂增强了血管反应.
- 针对H2Sn途径为血管疾病提供了潜在的治疗策略.
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