中性粒细胞对于心力衰竭中不良的心脏重塑是不可或缺的
Sergey Antipenko1, Nicolas Mayfield1, Miki Jinno1
1Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA.
Journal of molecular and cellular cardiology
|February 22, 2024
概括
中性粒细胞通过促进心脏中的炎症和组织损伤来加剧心力衰竭. 在心力衰竭的小鼠模型中,减少保护心脏重塑和纤维化的中性粒细胞.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 病理生理学 病理生理学
背景情况:
- 持续的免疫激活是左心室 (LV) 功能障碍和心力衰竭 (HF) 中不良重塑的关键驱动因素.
- 中性粒细胞在慢性缺血性心力衰竭的进展中的特定作用仍然不明,尽管它们在急性心肌梗塞 (MI) 中的已知功能.
研究的目的:
- 调查中性粒细胞在缺血性心肌病的进展中的重要性.
- 确定中性粒细胞枯竭对慢性心力衰竭小鼠模型中的心脏重塑和纤维化的影响.
主要方法:
- 利用老鼠模型的慢性心力衰竭诱导永久的冠状动脉绑定和大心肌梗塞 (MI).
- 量化中性粒细胞的产生,水平和激活在失败的心肌,血液,脏和骨髓中.
- 评估了中性粒细胞外细胞陷 (NET) 的形成和活动在体外和体内.
- 采用基于抗体和基因的方法来减少中性粒细胞的数量.
- 分析了来自人类急性不补偿性心力衰竭患者的血环境.
主要成果:
- 中性粒细胞在失败的心肌中显著更多,在心力衰竭 (HF) 系统性小鼠中显著更多,骨髓颗粒形成增加.
- 在HF中观察到中性细胞化学吸引化学基因 (CXCL1,CXCL5) 的心肌表达升高,以及循环中的化学性因子增加.
- 在HF小鼠中检测到中性粒细胞外细胞陷 (NET) 活动增加和循环NET.
- 中性粒细胞枯竭有效地废除了LV重塑和纤维化在HF中期和后期阶段的进展.
- 来自人类急性失补偿性HF患者的血促进了中性粒细胞贩运,反映了小鼠模型中的发现.
结论:
- 中性粒细胞在缺血性心肌病变的病理生物学中发挥着关键的,损伤组织的作用.
- 中性粒细胞及其细胞毒性产物有助于慢性心力衰竭中的不良心脏重塑和纤维化.
- 中性粒细胞是心力衰竭中免疫调节策略的有希望的治疗点.
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