急性心肌梗死的空间多组学揭示免疫细胞通过心内膜浸润。

IF 10.8 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Florian Wünnemann, Florian Sicklinger, Kresimir Bestak, Jose Nimo, Tobias Thiemann, Junedh M Amrute, Mathias Nordbeck, Niklas Hartmann, Miguel A Ibarra-Arellano, Jovan Tanevski, Margot Chazotte, Clara Heine, Norbert Frey, Kory J Lavine, Fabian Coscia, Julio Saez-Rodriguez, Florian Leuschner, Denis Schapiro
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引用次数: 0

摘要

心肌梗死(MI)仍然是世界范围内死亡的主要原因。尽管已经确定不同细胞类型之间的复杂相互作用决定了心肌梗死后的整体愈合反应,但组织结构的确切变化仍然知之甚少。在这项研究中,我们使用基于成像的转录组学(分子制图)和基于抗体的高复用成像(顺序免疫荧光)相结合,生成了小鼠心肌梗死急性期的综合细胞图谱。这使我们能够评估细胞类型组成和亚细胞分辨率随时间的变化。我们观察到白细胞通过心内膜向梗死心脏募集,并使用深度视觉蛋白质组学(Deep Visual Proteomics, DVP)进行了无偏倚的空间蛋白质组学分析,以探讨其潜在机制。DVP发现心肌梗死后24小时von Willebrand factor (vWF)是一种上调的炎症介质,功能性阻断vWF可减少心肌梗死后C-C趋化因子受体2 (Ccr2)阳性单核细胞的浸润,并使心功能恶化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Spatial multiomics of acute myocardial infarction reveals immune cell infiltration through the endocardium.

Myocardial infarction (MI) continues to be a leading cause of death worldwide. Even though it is well established that the complex interplay between different cell types determines the overall healing response after MI, the precise changes in the tissue architecture are still poorly understood. In this study, we generated an integrative cellular map of the acute phase after murine MI using a combination of imaging-based transcriptomics (Molecular Cartography) and antibody-based highly multiplexed imaging (Sequential Immunofluorescence). This enabled us to evaluate cell type compositions and changes at subcellular resolution over time. We observed the recruitment of leukocytes to the infarcted heart through the endocardium and performed unbiased spatial proteomic analysis using Deep Visual Proteomics (DVP) to investigate the underlying mechanisms. DVP identified von Willebrand factor (vWF) as an upregulated mediator of inflammation 24 hours after MI, and functional blocking of vWF reduced the infiltration of C-C chemokine receptor 2 (Ccr2)-positive monocytes and worsened cardiac function after MI.

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