Abstract
Background
Mesenchymal stromal cells (MSCs) have been implicated in the development and progression of myocardial diseases. However, the role of extracellular vesicles (EVs) secreted from human MSCs (hMSCs) of epicardial fat (eFat) in the pathogenesis of ischemic heart disease (IHD) has never been studied.
Purpose
We sought to characterize EVs from eFat-hMSCs of patients with and without IHD.
Methods
We collected eFat specimens from 12 patients with (n=7) and without (n=5) IHD who underwent open heart surgery. We isolated and cultured hMSCs by enzymatic digestion and adherence to plastic. EVs were separated from the culture media by differential ultra-centrifugation. We assessed EV size and structure by electron microscopy and nanoparticle tracking analysis. Finally, we evaluated the proteomic profile of EVs from ischemic and non-ischemic patients by mass spectrometry.
Results
eFat-hMSCs from ischemic patients, secreted higher amounts of small EVs (size range of 70–200 nm) compared with non-ischemic controls (Figure 1A+B). Proteomic analysis revealed over 1,000 proteins inside isolated EVs. We identified 13 proteins that were significantly differentially expressed between patients with and without IHD, including apolipoprotein E, transforming growth factor-β and collagen α-1 (Figure 1C). We performed an enrichment analysis which showed that EVs from eFat-hMSCs from ischemic patients encapsulated functional protein networks associated with immune activation. Unlike IHD patients, EVs from non-ischemic patients carried functional protein networks that regulate angiogenesis.
Conclusions
eFat-hMSCs of patients with IHD secrete higher amounts of small EVs with a unique proteomic signature related to immune activation. EVs derived from eFat-hMSCs should be further studied for their potential role in the initiation and progression of cardiovascular diseases, such as coronary artery disease, heart failure and arrhythmias.
Figure 1
Funding Acknowledgement
Type of funding source: None
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