Plasma Concentrations of Extracellular Vesicles Are Decreased in Patients with Post-Infarct Cardiac Remodelling

Simple Summary A heart attack may lead to the remodelling of the cardiac muscle, which negatively affects patient's prognosis. At present, the mechanisms of cardiac remodelling remain unclear. In patients with heart attack, many body cells become activated and release small particles, called extracellular vesicles, which can either aggravate cardiac injury, or contribute to healing of heart muscle. In our study, we hypothesized that the concentrations of these small particles in plasma allow to determine which patients will experience remodelling of the cardiac muscle after the heart attach. We found that concentrations of extracellular vesicles from endothelial cells, erythrocytes and platelets, measured directly the heart attack, were lower in patients who developed cardiac remodelling 6 months later, compared to patients who had no remodelling. Vesicles from endothelial cells and erythrocytes allowed to determine remodelling independently of other clinical features. Hence, decreased concentrations of these vesicles may on one hand be a sign of inappropriate cardiac repair mechanisms, and on the other hand may allow to identify patients, who will develop cardiac remodelling after the heart attack. Background, the mechanisms underlying left ventricular remodelling (LVR) after acute myocardial infarction (AMI) remain obscure. In the course of AMI, blood cells and endothelial cells release extracellular vesicles (EVs). We hypothesized that changes in EV concentrations after AMI may underlie LVR. Methods, plasma concentrations of EVs from endothelial cells (CD146+), erythrocytes (CD235a+), leukocytes (CD45+), platelets (CD61+), activated platelets (P-selectin+), and EVs exposing phosphatidylserine after AMI were determined by flow cytometry in 55 patients with the first AMI. LVR was defined as an increase in left ventricular end-diastolic volume by 20% at 6 months after AMI, compared to baseline. Results, baseline concentrations of EVs from endothelial cells, erythrocytes and platelets were lower in patients who developed LVR (p <= 0.02 for all). Concentrations of EVs from endothelial cells and erythrocytes were independent LVR predictors (OR 8.2, CI 1.3-54.2 and OR 17.8, CI 2.3-138.6, respectively) in multivariate analysis. Combining the three EV subtypes allowed to predict LVR with 83% sensitivity and 87% specificity. Conclusions, decreased plasma concentrations of EVs from endothelial cells, erythrocytes and platelets predict LVR after AMI. Since EV release EVs contributes to cellular homeostasis by waste removal, decreased concentrations of EVs may indicate dysfunctional cardiac homeostasis after AMI, thus promoting LVR.

Automated summary

After a heart attack, decreased plasma concentrations of extracellular vesicles from endothelial cells, erythrocytes and platelets may predict left ventricular remodelling, potentially indicating dysfunctional cardiac repair mechanisms and aiding in the identification of patients at risk for developing cardiac remodelling.