Plasma-derived extracellular vesicles contain predictive biomarkers and potential therapeutic targets for myocardial ischemic injury

Myocardial infarction (MI) triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, necessary for myocardial healing. Timely repression of inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains challenging. The ability of EVs to trigger a functional response upon delivery of carried bioactive cargos, have made them clinically attractive diagnostic biomarkers and vectors for therapeutic interventions.

Using label-free quantitative proteomics approach, researchers from the Nanyang Technological University, Singapore compared the protein cargo of plasma EVs between patients with MI and from patients with stable angina (NMI). They report, for the first time, the proteomics profiling on 252 EV proteins that were modulated with >1.2-fold after MI. They identified six up-regulated biomarkers with potential for clinical applications; these reflected post-infarct pathways of complement activation. This novel biomarker panel was validated in 43 patients using antibody-based assays.

Schematic workflow showing the label-free quantitative proteomic analysis of extracellular vesicles (EVs) isolated from the pooled plasma of patients with stable angina (NMI) or myocardial infarction (MI).

The researchers further present that EV-derived fibrinogen components were paradoxically down-regulated in MI, suggesting that a compensatory mechanism may suppress post-infarct coagulation pathways, indicating potential for therapeutic targeting of this mechanism in MI. Taken together, these data demonstrated that plasma EVs contain novel diagnostic biomarkers and therapeutic targets that can be further developed for clinical use to benefit patients with coronary artery diseases.