DSCAML1+ extracellular vesicles revealed by single-vesicle proteomics as a novel biomarker and therapeutic target in myocardial infarction

Abstract The early and accurate diagnosis of acute myocardial infarction (AMI) remains a significant clinical challenge. To this end, we profiled the surface proteome of individual plasma extracellular vesicles (EVs) from AMI patients using single-vesicle sequencing, aiming to identify disease-associated alterations with diagnostic and therapeutic potential. Profiling the EV surface proteome across healthy controls (HC), coronary artery stenosis (CAS), and AMI revealed 21 differentially expressed proteins (DEPs), 11 of which were uniquely associated with AMI compared to HC. Notably, these included elevated levels of DSCAML1, CR1, ACE2, FN1, CDH15, and C5b‑9. EVs were subsequently stratified into 17 subpopulations, with clusters 1, 8, and 9 characterized by DSCAML1, ALCAM, and CR1, respectively, and showing the highest enrichment in AMI. We further demonstrated that plasma EVs from AMI patients (AMI-EVs) promote cardiomyocyte proliferation and endothelial cell activity in vitro, followed by the finding that the DSCAML1-enriched subpopulation (DSCAML1-EVs) enhances myocardial repair and angiogenesis both in vitro and in vivo, with mechanistic studies implicating the EREG/ERK pathway in these effects. In summary, DSCAML1-positive EVs show dual potential as both a diagnostic biomarker for AMI and a therapeutic target for improving post‑infarction prognosis, providing insight into the translational potential of EV‑based strategies in precision cardiology. Graphical Abstract