Characterization of Circulating Vesicles of Complicated and Uncomplicated Systemic Sclerosis Patients and Their Role in Vascular Dysfunction

Extracellular vesicles (EVs) could be involved in the onset of systemic sclerosis (SSc) through the modulation of vascular function. Anyway, available data are contradictory, and further investigation would be necessary to clarify this aspect. Here, we characterized circulating EVs isolated from SSc patients and evaluated their effects on human vascular endothelial cells (HUVECs) and smooth muscle cells. In EVs from 13 complicated and 27 uncomplicated SSc patients and five healthy controls (HCs), we analyzed the size, concentration, and surface marker expression. In addition, EVs were used to stimulate HUVECs, and we evaluated cell viability, mitochondrial membrane potential, and nitric oxide (NO) and mitochondrial reactive oxygen species (MitoROS) release. In smooth muscle cells, the effects of EVs on calcium movement were examined. The results showed that the EVs of SSc patients expressed markers of T-lymphocyte/platelet/endothelial cell origin and were larger and more concentrated than those from HCs. In addition, the EVs of SSc patients reduced cell viability and mitochondrial membrane potential and increased NO and MitoROS release in HUVECs and intracellular calcium in smooth muscle cells. In conclusion, we found a specific pattern for EVs isolated from SSc patients, which could have a pathogenic role through direct actions on endothelial and smooth muscle cells.