BET抑制阻断炎症引起的心脏功能障碍和SARS-CoV-2感染
Richard J Mills1, Sean J Humphrey2, Patrick R J Fortuna1
1QIMR Berghofer Medical Research Institute, Brisbane 4006, QLD, Australia.
Cell
|April 3, 2021
概括
COVID-19 通过炎症引起心脏损伤. 在模型中,布罗姆多马因和外部家族抑制剂 (BETi) 显示出预防心脏功能障碍和死亡的前景,提供潜在的治疗策略.
科学领域:
- 心脏病学
- 病毒学
- 分子生物学
背景情况:
- COVID-19 与心脏损伤和死亡率有关.
- 机制包括直接的病毒感染或由炎症引起的心脏功能障碍.
- 确定治疗点对于管理COVID-19对心脏的影响至关重要.
研究的目的:
- 阐明COVID-19引起的心脏功能障碍的机制.
- 识别潜在的抗COVID-19心脏保护药物.
主要方法:
- 使用人类心脏器官 (hCO) 和K18-hACE2小鼠模型.
- 使用蛋白组学和单核RNA测序.
- 研究炎症刺激和BET抑制剂的影响.
主要成果:
- 一个"细胞因子风暴" (干扰素马,干扰素1β,多I:C)) 诱导的腹功能障碍.
- 在hCOs和小鼠模型中观察到含基蛋白4的激活和病毒反应.
- BET抑制剂恢复了hCOs的心脏功能,并预防了小鼠的死亡.
- BETi降低了病毒基因转录,ACE2表达和心肌细胞感染.
结论:
- 包括apabetalone在内的BETi有效抵消COVID-19引起的心脏功能障碍和死亡率.
- 贝蒂代表了预防COVID-19患者心脏损伤的有希望的治疗候选者.
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