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

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.