Abstract Body: Background: Small extracellular vesicles (sEVs) from blood samples of patients with cerebral aneurysms (CA) have been used as a biomarker for CA. However, biological function of sEVs in CA has not been studied. We tested the hypothesis that plasma sEVs from patients with CA impair cerebral endothelial cell (CEC) function.

Methods: Plasma sEVs were isolated using ultracentrifugation from venous and arterial blood of patients with CA undergoing endovascular treatment. Size and marker proteins of sEVs were characterized. Human CECs were treated with sEVs at 1x10⁸ particles/ml. The effects of sEVs on CEC permeability and angiogenesis were measured by trans-endothelial and tube formation assays, respectively. One-way ANOVA was used for statistical analysis.

Results: Ten patients, 6 with non-ruptured CA and 4 with ruptured CA, ranging in age from 51-88 years old were studied. There were no significant differences in sEV sizes and protein markers between non-ruptured and ruptured CA (141 ± 6 nm vs 144 ± 2 nm). The permeability assay showed that compared to controls, sEVs derived from arterial samples (asEVs) from ruptured and non-ruptured CA significantly increased CEC leakage (116 ± 7 and 119 ± 14 vs 101 ± 6 control, respectively, p<0.05). The angiogenic assay showed that venous sEVs (vsEVs), but not asEVs, of non-ruptured CA, significantly (p<0.05) increased vascular branches (14 ± 6 vs 6 ± 3 control), however, both vsEVs and asEVs of ruptured CA robustly increased the branch numbers (13 ± 7, and 13 ± 5 vs 6 ± 3 control, respectively, p<0.05).

Conclusions: Increased CEC permeability and vascular branches are highly related to blood brain barrier (BBB) damage and angiogenesis, respectively. Thus, our data suggest that sEVs from CA could damage the BBB and promote angiogenesis, which provides new insights into the role of sEVs in mediating CA progression.