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.
Authors
- Jose Nimo (ORCID: https://orcid.org/0000-0002-1565-7799)
- Junedh Amrute (ORCID: https://orcid.org/0000-0002-6851-0168)
- Kory J. Lavine (ORCID: https://orcid.org/0000-0003-1948-9945)
- Julio Sáez-Rodríguez (ORCID: https://orcid.org/0000-0002-8552-8976)
- Norbert Frey (ORCID: https://orcid.org/0000-0001-7611-378X)
- C. Heine
- Margot Chazotte
- Jovan Tanevski (ORCID: https://orcid.org/0000-0001-7177-1003)
- Florian Wünnemann (ORCID: https://orcid.org/0000-0002-0978-6076)
- Florian Leuschner (ORCID: https://orcid.org/0000-0003-1157-474X)
- Denis Schapiro (ORCID: https://orcid.org/0000-0002-9391-5722)
- Miguel A. Ibarra-Arellano (ORCID: https://orcid.org/0000-0001-8411-4854)
- Kresimir Bestak (ORCID: https://orcid.org/0009-0009-8245-9846)
- Fabian Coscia (ORCID: https://orcid.org/0000-0002-2244-5081)
- Tobias Thiemann
- Mathias Nordbeck (ORCID: https://orcid.org/0009-0003-0392-6685)
- Florian Sicklinger (ORCID: https://orcid.org/0009-0004-6707-1695)
- Niklas Hartmann (ORCID: https://orcid.org/0009-0009-1799-7162)
Institutions
- European Bioinformatics Institute (GB)
- Washington University in St. Louis (US)
- Max Delbrück Center (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Humboldt-Universität zu Berlin (DE)
- German Centre for Cardiovascular Research (DE)
- German Center for Lung Research (DE)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Nature Cardiovascular Research
- Published
- 2025-10-03
- DOI
- https://doi.org/10.1038/s44161-025-00717-y
- Citations
- 6
- Primary Topic
- Atherosclerosis and Cardiovascular Diseases
- Type
- article
- Field-Weighted Citation Impact
- 4.78