*these authors contributed equally

A multidisciplinary team led by researchers at the Goethe University Frankfurt has uncovered a previously unrecognized immune-regulating role of cardiac endothelial cells after myocardial infarction — revealing a new cellular player that may shape post-heart-attack inflammation and healing.

Using single-cell RNA sequencing and spatial transcriptomics in mice and humans, the team identified a transient endothelial cell state emerging within days of infarction, termed immunomodulatory endothelial cells (IMECs). These cells originate from resident cardiac endothelium but adopt a hybrid endothelial–myeloid transcriptional profile, including high expression of MHC class II molecules, RUNX1, and pro-inflammatory cytokines such as IL-6 and IL-12.

In vitro, the combination of TGF-β, IL-1β, and IFN-γ reproduced the IMEC signature, with IFN-γ playing a pivotal role in shifting cells toward an immunomodulatory rather than mesenchymal fate. Functionally, IMECs activate T cells via paracrine cytokine signaling and co-localize with T cells in both mouse and human infarct border zones.

In vivo, blocking IFN-γ signaling specifically in endothelial cells after myocardial infarction prevents this shift and improves cardiac recovery, underscoring the pathological potential of this cell state.

The researchers conclude that IMECs can transiently act as immune activators after heart injury, amplifying inflammatory responses, and that targeting their induction or function could represent a promising strategy to modulate post-infarction immunity and enhance cardiac repair.

Find the full article here: https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.125.326145?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed