肝血管神经髓质衍生的生生长因子保护肺动脉高血压中的内皮功能障碍
bioRxiv : the preprint server for biology
|November 19, 2025
概括
骨髓衍生生长因子 (MYDGF) 缺乏可能会使肺动脉高血压 (PAH) 恶化. 虽然MYDGF在预防炎症方面表现有前途,但在人类中,高水平矛盾地与较差的PAH结果有关.
科学领域:
- 心血管生物学 心血管生物学
- 肺高血压研究 肺高血压研究
- 肝脏的血管氨基酸.
背景情况:
- 骨髓衍生生长因子 (MYDGF) 是一种具有已知的保护性血管作用的肝血管.
- 在肺动脉高血压 (PAH) 中MYDGF的作用仍然未被探索.
- 这项研究调查了MYDGF在PAH病变发生过程中的参与及其治疗潜力.
研究的目的:
- 确定肝脏MYDGF在实验性PAH中的作用.
- 研究复合MYDGF对肺内皮细胞的影响.
- 分析人类PAH队列中的MYDGF水平,并将其与疾病严重程度和结果相关联.
主要方法:
- 使用苏根低氧 (SuHx) 鼠标模型来评估MYDGF表达和肺VCAM-1.
- 暴露在巨受条件介质中的人类肝脏鼻状内皮细胞,然后用重组MYDGF进行治疗.
- 分析了两个独立的人类PAH队列 (PHiNE和Servetus) 的血MYDGF水平,使用蛋白质组学,与临床数据相关.
主要成果:
- 在SuHx大鼠模型中,肝脏MYDGF表达减少,而肺部VCAM-1增加.
- 再组合MYDGF通过MAP4K4-NFκB信号传递来保护肺动脉内皮细胞的炎症激活.
- 血MYDGF在PAH患者中升高,但随着肝硬度下降,与较高的肺血管抵抗相关;较高的MYDGF与Servetus队列中的死亡率相关.
结论:
- 在实验性PAH中观察到肝脏MYDGF缺乏,MYDGF显示有潜力减轻肺内皮炎症.
- 人类数据揭示了一个复杂的,矛盾的关联,其中循环MYDGF的升高与不良PAH结果相关.
- MYDGF作为一种潜在的新型肝血管因,将肝功能障碍,全身炎症和肺血管疾病联系起来.
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