Circulating plasma exosomes reflect the severity of myocardial damage in STEMI patients

Abstract

Exosomes are small extracellular vesicles involved in intercellular communication and they contribute to inflammation, coagulation and vascular injury. Exosomes have demonstrated a great potential as diagnostic markers of disease, however their ability to reflect myocardial damage assessed by Cardiac Magnetic Resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) is still unknown. To fill this gap, plasma exosomes were isolated from 42 STEMI patients treated by primary percutaneous coronary intervention (pPCI) and evaluated by CMR between days 3 and 6. Exosome concentration and size were measured by Nanoparticle Tracking Analysis, surface epitopes by flow cytometry, and platelet marker expression by ELISA kit. Exosome levels were greater in patients with anterior STEMI (p = 0.0001), with the culprit lesion located in LAD (p = 0.045), and in those who underwent late revascularization (p = 0.038). A smaller exosome size was observed in patients with a low myocardial salvage index (MSI, p = 0.014). Exosomes of patients with microvascular obstruction (MVO) had smaller dimension (p < 0.002) and lower expression of the platelet marker CD41–CD61 (p = 0.039). Exosome size and CD41–CD61 expression were independent predictors of MVO/MSI (OR [95% CI]: 0.93 [0.87–0.98] and 0.04 [0–0.61], respectively). In conclusion, we reported for the first time the ability of exosomes isolated a few days after STEMI to reflect myocardial damage. In particular, the exosome size and expression of the platelet marker CD41–CD61, likely reflecting the level of circulating platelet-derived exosome, were independent predictors of MVO and low MSI that are both predictors of short-term prognosis of acute STEMI after pPCI treatment and are key variables for risk-stratification of patients after STEMI. This finding paves the way for the development of a new strategy for the timely identification of high-risk patients and their treatment optimization.