Circulating extracellular vesicles in subarachnoid hemorrhage patients: characterization and cellular effects

Circulating extracellular vesicles (EVs) may play a pathophysiological role in the onset of complications of subarachnoid hemorrhage (SAH) potentially contributing to the development of vaso-spasm (VP). In this study we aimed to characterize circulating EVs in SAH patients and examine their effects on endothelial and smooth muscle cells (SMC). In a total of 18 SAH patients, 10 with VP (VP), 8 without VP (NVP), and 5 healthy controls (HC), clinical variables were recorded at different time points. EVs isolated from plasma samples were characterized and used to stimulate human vascular endothelial cells (HUVEC) and SMC. We found that EVs from SAH patients ex-pressed markers of T-lymphocytes and platelets, had a larger size and a higher concentration compared to those from HC. Moreover, EVs from VP patients reduced cell viability and mitochondrial membrane potential in HUVEC and increased oxidants and nitric oxide (NO) release. Furthermore, EVs from SAH patients increased intracellular calcium level in SMC. Altogether, our findings reveal an altered pattern of circulating EVs in SAH patients, suggesting their pathogenic role in promoting endothelial damage and enhancing smooth muscle reactivity. These results have significant implications for the use of EVs as potential diagnostic/prognostic markers and therapeutic tools in SAH management.