机械拉伸降低了心力衰竭中的纤维细胞激活,减少了喷射分数
Daniel N Silverman1, Ahmed A Ismail2, Lauren Wakefield2
1Medical University of South Carolina, Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, SC; Ralph H. Johnson Veterans Administration Health Care System, Department of Medicine, Division of Cardiology, Charleston, SC.
概括
脉动机械支,模仿自然的心脏功能,可以通过减少硬度和增加循环拉伸来逆转心力衰竭 (HF) 中的纤维细胞激活. 这种方法为HF患者提供了潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 生物医学工程 生物医学工程
- 纤维细胞生物学 纤维细胞生物学
背景情况:
- 由于纤维细胞激活,心力衰竭 (HF) 的特征是心脏纤维化增加.
- 目前的非脉动左心室辅助装置 (LVAD) 支持使血液动力负荷正常化,但不会逆转已建立的纤维化.
- 在HF中,纤维细胞表型尽管负载正常化,但仍然存在,这表明细胞内在的变化.
研究的目的:
- 为了研究是否减少负载结合循环拉伸在体外可以减弱纤维细胞激活.
- 探索脉动性LVAD疗法的潜力,以逆转HF中的纤维细胞激活.
主要方法:
- 人类心脏纤维细胞 (HCFs) 从减少喷射率 (HFrEF) 患者和对照捐赠者中分离出来.
- 在模仿正常 (1 kPa) 或HFrEF (10 kPa) 心肌硬度的基板上培养HCF.
- 细胞经历了48小时的循环拉伸或静态条件,随后对蛋白质生产和基因表达进行了分析.
主要成果:
- HFrEF心肌表现出明显高于对照组的原蛋白含量.
- 在刚性基板 (10 kPa) 上培养的HFrEF HCFs在不拉伸的原蛋白生产中没有差异.
- 在正常化的硬度基板 (1kPa) 上循环拉伸显著降低了HFrEF HCF中的原蛋白,TIMP1和αSMA生产,将基因表达途径转移到控制水平.
结论:
- 正常化的基质刚度与循环拉伸相结合,有效地减弱了初级HCF中的纤维细胞激活.
- 这项研究确定了参与逆转HF纤维细胞表型的机制性途径.
- 这些发现支持脉动性LVAD疗法在治疗HF心脏纤维化方面的潜力.
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