Defining the cardiac fibroblast secretome in the healthy and infarcted mouse heart

Jasmin Bahr; Gereon Poschmann; Andreas Jungmann; Martin Busch; Zhaoping Ding; Jens Vogt; Ria Zalfen; Julia Steinhausen; Arlen Aurora Euan Martínez; Thorsten Wachtmeister; Daniel Rickert; Tobias Lautwein; Christina Alter; Junedh Amrute; Kory J. Lavine; Karl Köhrer; Bodo Levkau; Patrick Most; Kai Stühler; Julia Hesse; Jürgen Schrader

doi:10.1038/s42003-025-08083-y

PhysiologyCommunications BiologyApr 29, 2025

Peer-reviewed journal article

Defining the cardiac fibroblast secretome in the healthy and infarcted mouse heart

Jasmin Bahr iD, Gereon Poschmann iD, Andreas Jungmann, Martin Busch iD, Zhaoping Ding iD, Jens Vogt iD, Ria Zalfen, Julia Steinhausen, Arlen Aurora Euan Martínez, Thorsten Wachtmeister iD, Daniel Rickert, Tobias Lautwein iD, Christina Alter iD, Junedh Amrute iD, Kory J. Lavine iD, Karl Köhrer iD, Bodo Levkau iD, Patrick Most iD, Kai Stühler iD, Julia Hesse iD, Jürgen Schrader iD

Abstract

Cardiac fibroblasts (CF) are key players after myocardial infarction (MI), but their signaling is only incompletely understood. Here we report a first secretome atlas of CF in control (cCF) and post-MI hearts (miCF), combining a rapid cell isolation technique with SILAC and click chemistry. In CF, numerous paracrine factors involved in immune homeostasis were identified. Comparing secretome, transcriptome (SLAMseq), and cellular proteome disclosed protein turnover. In miCF at day 5 post-MI, significantly upregulated proteins included SLIT2, FN1, and CRLF1 in mouse and human samples. Comparing the miCF secretome at day 3 and 5 post-MI showed the dynamic nature of protein secretion. Specific in-vivo labeling of miCF proteins via biotin ligase TurboID using the POSTN promotor mirrored the in-vitro data. In summary, we have identified numerous paracrine factors specifically secreted from CF in mice and humans. This secretome atlas may lead to new biomarkers and/or therapeutic targets for the activated CF.

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