TY - JOUR
T1 - Spatial multiomics of acute myocardial infarction reveals immune cell infiltration through the endocardium
AU - Wünnemann, Florian
AU - Sicklinger, Florian
AU - Bestak, Kresimir
AU - Nimo, Jose
AU - Thiemann, Tobias
AU - Amrute, Junedh M.
AU - Nordbeck, Mathias
AU - Hartmann, Niklas
AU - Ibarra-Arellano, Miguel A.
AU - Tanevski, Jovan
AU - Chazotte, Margot
AU - Heine, Clara
AU - Frey, Norbert
AU - Lavine, Kory J.
AU - Coscia, Fabian
AU - Saez-Rodriguez, Julio
AU - Leuschner, Florian
AU - Schapiro, Denis
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/10
Y1 - 2025/10
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105017865429
U2 - 10.1038/s44161-025-00717-y
DO - 10.1038/s44161-025-00717-y
M3 - Article
C2 - 41044418
AN - SCOPUS:105017865429
SN - 2731-0590
VL - 4
SP - 1345
EP - 1362
JO - Nature Cardiovascular Research
JF - Nature Cardiovascular Research
IS - 10
ER -