This study uses single-cell RNA sequencing to investigate the kinetics and individual cellular responses of endothelial cells (ECs) after myocardial infarction (MI). It reveals a time-dependent switch in EC proliferation and inflammation, along with transient changes in metabolic gene signatures. Trajectory analysis shows that most ECs transiently acquire a mesenchymal state 3–7 days post-MI, reverting to baseline by day 14. Lineage tracing confirms this transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures. The findings suggest that ECs undergo transient mesenchymal activation and metabolic adaptation after MI, facilitating cell migration and clonal expansion for vascular regeneration.

Lukas S. Tombor, David John, Simone F. Glaser, Guillermo Luxán, Elvira Forte, Milena Furtado, Nadia Rosenthal, Nina Baumgarten, Marcel H. Schulz, Janina Wittig, Eva-Maria Rogg, Yosif Manavski, Ariane Fischer, Marion Muhly-Reinholz, Kathrin Klee, Mario Looso, Carmen Selignow, Till Acker, Sofia-Iris Bibli, Ingrid Fleming, Ralph Patrick, Richard P. Harvey, Wesley T. Abplanalp, Stefanie Dimmeler