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第二个心脏场衍生细胞有助于血管素II介导的上升性动脉病变
Hisashi Sawada1,2,3,4, Yuriko Katsumata5,6, Hideyuki Higashi
1Saha Cardiovascular Research Center (H.S., J.Z.C., M.K.F., J.J.M., D.A.H., D.L.R., H.S.L., A.D.), University of Kentucky, Lexington.
Circulation
|February 10, 2022
概括
第二心场 (SHF) 衍生细胞对于保持上升大动脉完整性至关重要. 它们在胸腔动脉病变中的作用涉及LRP1和TGF-β信号,影响PAI1水平.
科学领域:
- 心血管生物学
- 发育生物学
- 血管生物学
背景情况:
- 上升性大动脉是动脉瘤和解剖的常见地点.
- 这一区域包含来自第二个心脏场 (SHF) 或心脏神经的中间和偶然细胞.
- 在易患胸部动脉病变的区域发现SHF衍生细胞.
研究的目的:
- 研究SHF衍生的细胞对上升性动脉病变的贡献.
- 确定SHF衍生细胞影响大动脉完整性的机制.
主要方法:
- 对人类胸部动脉动脉病组织和输入血管素II (AngII) 的小鼠模型的分析.
- 上升动脉的蛋白质组和单细胞转录组分析.
- 在SHF衍生的细胞中,LRP1或TGF-β受体类型2 (Tgfbr2) 的遗传删除.
主要成果:
- 在小鼠中输注AngII模仿了人类大动脉病变的分布,并影响了SHF衍生的细胞基因表达.
- 在SHF衍生的细胞中LRP1的缺失加剧了AngII诱导的大动脉瘤和破裂.
- 特定于SHF的Tgfbr2缺失导致胚胎致死性;PAI1被确定为SHF衍生细胞上调的关键蛋白.
结论:
- 由SHF衍生的细胞对于维持上升性大动脉的血管完整性至关重要.
- 在SHF衍生细胞中的LRP1和TGF-β信号通路对大动脉健康至关重要.
- 大动脉PAI1水平的增加与SHF衍生的细胞功能障碍有关.
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