Sox17 protects human brain microvascular endothelial cells from AngII-induced injury by regulating autophagy and apoptosis

Intracranial aneurysm (IA), is a localized dilation of the intracranial arteries, the rupture of which is catastrophic. Hypertension is major IA risk factor that mediates endothelial cell damage. Sox17 is highly expressed in intracranial vascular endothelial cells, and GWAS studies indicate that its genetic alteration is one of the major genetic risk factors for IA. Vascular endothelial cell injury plays a vital role in the pathogenesis of IA. The genetic ablation of Sox17 plus hypertension induced by AngII can lead to an increased incidence of intracranial aneurysms had tested in the previous animal experiments. In order to study the underlying molecular mechanisms, we established stable Sox17-overexpressing and knockdown cell lines in human brain microvascular endothelial cells (HBMECs) first. Then flow cytometry, western blotting, and immunofluorescence were employed. We found that the knockdown of Sox17 could worsen the apoptosis and autophagy of HBMECs caused by AngII, while overexpression of Sox17 had the opposite effect. Transmission electron microscopy displayed increased autophagosomes after the knockdown of Sox17 in HBMECs. The RNA-sequencing analysis shown that dysregulation of the Sox17 gene was closely associated with the autophagy-related pathways. Our study suggests that Sox17 could protect HBMECs from AngII-induced injury by regulating autophagy and apoptosis.

Automated summary

Intracranial aneurysm is a localized dilation of the intracranial arteries, and its rupture can be catastrophic. Hypertension mediates endothelial cell damage, which is a major risk factor for intracranial aneurysm. Sox17 is highly expressed in intracranial vascular endothelial cells and its genetic alteration is a major genetic risk factor for intracranial aneurysm. In this study, we found that knockdown of Sox17 worsened AngII-induced apoptosis and autophagy in human brain microvascular endothelial cells, while overexpression of Sox17 had the opposite effect.