髓状细胞的招募通过无菌炎症驱动HFpEF的右心室功能障碍
Lara Jaeschke1,2,3,4, Ceren Koçana1,2,3,4, Alexandra Maria Chitroceanu2,4,5
1Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany.
bioRxiv : the preprint server for biology
|December 3, 2025
概括
白细胞失调有助于右心室功能障碍 (RVD) 在心力衰竭中保持喷射分数 (HFpEF). 准髓状细胞在小鼠模型中改善了RV功能,这表明HFpEF-RVD的治疗标.
科学领域:
- 心脏病学 心脏病学
- 免疫学 免疫学 免疫学
- 翻译医学是一种翻译医学.
背景情况:
- 右心室功能障碍 (RVD) 在心力衰竭中常见,但其机制,特别是白细胞的作用尚不清楚.
- 现有的研究集中在HFpEF的左心室扩张性功能障碍上,在了解RVD病变发生方面存在差距.
- 缺乏合适的小型动物模型,阻碍了对白细胞参与HFpEF相关RVD的研究.
研究的目的:
- 建立一个HFpEF的小鼠模型,开发RVD.
- 通过动物模型和人类队列,研究HFpEF中白细胞和RVD之间的机制联系.
- 为了确定骨髓细胞是否因果性地导致HFpEF中的RV重塑.
主要方法:
- 建立了一种使用L-NAME和高脂肪饮食的小鼠HFpEF模型,有或没有慢性缺氧,以诱导双心脏功能障碍和RVD.
- 评估心脏功能使用心声回声和侵入性血液动力学.
- 通过流细胞计和蛋白质组分析分析心脏组织中的髓状细胞群.
- 在小鼠中利用了髓状细胞枯竭 (PLX-5622) 和命运映射.
- 检查了来自HFpEF患者的RV活检,检查炎症和纤维化标志物.
主要成果:
- 在HFpEF模型中表现出LV的透功能障碍,RV的增大和RVD.
- 在HFpEF小鼠的RV中观察到白细胞,单细胞和巨细胞数量的增加,其中单细胞衍生的巨细胞是主要来源.
- 蛋白质组分析显示,RV组织中的先天性免疫激活,化疗和ECM组织蛋白增加.
- 骨髓细胞枯竭在HFpEF模型中改善了RV缩压.
- 在RV活检中,HFpEF患者的循环单细胞和炎症/纤维细胞标志物增加.
结论:
- 失调的髓状细胞动态与HFpEF相关的RVD有关.
- 白细胞,特别是巨细胞,在HFpEF中RVD的发病过程中发挥着直接作用.
- 准髓状细胞可能为与HFpEF相关的RVD提供治疗策略.
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