外化素H4通过诱导溶性细胞死亡来调节慢性炎症
Carlos Silvestre-Roig1,2,3, Quinte Braster4,5,6, Kanin Wichapong7
1Institute for Cardiovascular Prevention (IPEK), LMU München, Munich, Germany. carlos.silvestre@med.uni-muenchen.de.
Nature
|May 3, 2019
概括
在动脉样硬化中,细胞外基因组H4会导致平滑肌肉细胞死亡和动脉损伤. 中和素H4可以防止细胞死亡,稳定动脉样损伤,并为慢性血管疾病提供潜在的治疗点.
科学领域:
- 心血管生物学
- 免疫学
- 细胞死亡机制
背景情况:
- 慢性炎症对全球健康造成重大负担.
- 非编程细胞死亡有助于慢性炎症,但其诱导和媒介尚不清楚.
- 动脉样硬化是导致死亡的主要原因,
研究的目的:
- 调查细胞外素H4在平滑肌肉细胞死亡和动脉样硬化的炎症中的作用.
- 在血管疾病中识别炎症的细胞和分子媒介.
- 探索针对希斯H4的潜在治疗策略
主要方法:
- 使用了动脉样硬化的小鼠模型.
- 研究了细胞外素H4与平滑肌细胞 (SMC) 之间的相互作用.
- 分析了中性粒细胞外陷 (NET) 的形成和基因素H4的释放.
- 评估了素H4中和对SMC死亡和斑块稳定性的影响.
主要成果:
- 细胞外基因素H4调解SMC的膜溶解,引发动脉组织损伤和炎症.
- 激活的SMC吸引中性粒细胞,导致含有核蛋白质的NET排放,如素H4.
- 素H4与SMC结合导致细胞死亡和斑块不稳定;其中和可以防止SMC死亡并稳定病变.
结论:
- 在慢性血管疾病中发现白细胞诱导细胞死亡的新形式.
- 细胞外基因素H4是SMC死亡和动脉硬化斑块不稳定的关键媒介.
- 针对细胞外的希斯H4为动脉样硬化和相关的慢性血管疾病提供了有前途的治疗途径.
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