Abstract Body: After myocardial infarction (MI), fibroblast proliferation and myofibroblast differentiation are largely driven by inflammation-primed, growth factor–dependent signaling cascades. While inhibition of these pathways can reduce pathological fibrosis, it often destabilizes scar formation and increases the risk of ventricular wall rupture, limiting clinical translation. Therefore, no therapies specifically target adverse remodeling without impairing scar integrity. Here, we identify a novel, targetable pathway that reduces fibrotic remodeling after ischemia without disrupting scar formation by targeting communication between cardiac stromal cells (CSC) with endothelial cells (EC) and fibroblasts. CSC play a critical role in supporting cardiac growth and structure, and their communication with other cell types is essential for effective myocardial repair following injury. After MI, CSC are recruited to the injury site, where the ischemic environment induces de novo expression of the glycoprotein Podoplanin (PDPN). We previously showed that CSC^PDPN+ populate the ischemic myocardium and communicate with immune cells by binding the PDPN receptor CLEC2 and by secreting small extracellular vesicles (sEV). Our preliminary data demonstrate that CSC^PDPN+ also influence EC and fibroblasts through sEV-mediated signaling and that the injection of CSC^PDPN+sEV into uninjured mouse hearts induces epicardial fibrosis and impairs cardiac function. Proteomic profiling revealed an exclusive enrichment of NOTCH1 and NOTCH1 processing machinery within the CSC^PDPN+sEV cargo, which are transferred from CSC^PDPN+ to recipient cells. In vitro, CSC^PDPN+sEV activate NOTCH1 signaling in EC and fibroblasts, promoting EndoMT and myofibroblast differentiation, whereas NOTCH1-null sEV fail to induce these responses. Pharmacological inhibition of NOTCH1 signaling attenuates these phenotypic transitions in vitro and improves cardiac function after MI in vivo. We conclude that CSC^PDPN+sEV–delivered NOTCH1 engages NOTCH ligands on EC and fibroblasts, driving fibrotic signaling and adverse remodeling after MI. Targeting this pathway represents a novel translational strategy to limit pathological fibrosis while preserving essential scar formation.