亚当-17活动及其与ACE2的关系:对严重的COVID-19的影响
Jiangming Sun1, Andreas Edsfeldt1,2,3, Joel Svensson4
1Cardiovascular Research-Translational Studies, Department of Clinical Sciences Malmö, Lund University, 205 02 Malmö, Sweden.
International journal of molecular sciences
|June 19, 2024
概括
增加的分解素和金属蛋白酶-17 (ADAM-17) 活性与严重的COVID-19有关,并可能影响血管氨酸转化酶2 (ACE2) 的分泌. 这表明ADAM-17,ACE2和COVID-19严重程度之间存在联系.
科学领域:
- 生物化学和分子生物学
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- 在COVID-19患者的解体素和金属蛋白酶-17 (ADAM-17) 活性方面存在有限的研究.
- 在COVID-19中,ADAM-17活性与膜结合的血管酶转化酶2 (mACE2) 脱落之间的关联尚未得到研究.
- 在SARS-CoV-2感染器官中ADAM-17和ACE2基因表达之间的关系需要调查.
研究的目的:
- 评估COVID-19患者细胞ADAM-17活动及其与疾病严重程度和死亡率的关联.
- 研究ADAM-17活性,可溶性ACE2 (sACE2) 水平,素,炎症标志物和肺损伤之间的关系.
- 根据不同组织的年龄和性别评估ADAM-17和ACE2基因表达模式.
主要方法:
- 利用了来自马萨诸塞州总医院COVID-19研究的数据 (306名COVID-19患者,78名对照).
- 计算了ADAM-17基质得分作为细胞ADAM-17活动的替代品.
- 分析了ADAM-17基质得分,COVID-19严重程度/死亡率,SACE2,renin,炎症标志物和肺损伤标志物之间的关联.
- 使用基因型-组织表达 (GTEx) 数据库检查了ADAM-17和ACE2基因表达.
主要成果:
- 增加的ADAM-17活性与COVID-19严重程度显著相关 (p = 0.001).
- ADAM-17活性显示出与死亡率增加相关的趋势 (p = 0.06).
- 溶性ACE2与ADAM-17基质得分呈现最强的正相关性,其次是雷宁,IL-6和肺损伤生物标志物.
- 在肺部,ADAM-17与ACE2基因表达比率最高.
结论:
- 较高的ADAM-17活性与严重的COVID-19相关.
- 研究结果表明,mACE2分泌 (通过ADAM-17),失调的氨酸-血管酶系统 (RAS) 和COVID-19中的免疫信号之间存在潜在的双向关系.
- 在ACE2和ADAM-17基因表达的组织特异性差异可能有助于肺部对SARS-CoV-2感染的易感性.
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