ETR silencing ameliorated neurovascular injury after SAH in rats through ERK/KLF4-mediated phenotypic transformation of smooth muscle cells.

Subarachnoid haemorrhage (SAH) is a devastating cerebrovascular disease which has a high morbidity and mortality. The phenotypic transformation of smooth muscle cells (SMCs) lead to neurovascular injury after SAH. However, the underlying mechanism remains unclear. In the present study, we aimed to investigate the potential role of ET-1/ETR on the phenotypic transformation of SMCs after SAH. The models of SAH were established in vivo and vitro. We observed ET-1 secretion by endothelial cells was increased, and the phenotypic transformation of SMCs was aggravated after SAH. Knocking down ETR inhibited the phenotypic transformation of SMCs, decreased the migration ability of SMCs in vitro. Moreover, Knocking down ETR ameliorated cerebral ischaemia and alleviated dysfunction of neurological function in vivo. In addition, Exogenous ET-1 increased the migration ability of SMCs and aggravated the phenotypic transformation of SMCs in vitro, which were partly reversed by the antagonist of Erk1/2 - SCH772984. Taken together, our results demonstrated that endothelial ET-1 aggravated the phenotypic transformation of SMCs after SAH. Knocking down ETR inhibited the phenotypic transformation of SMCs through ERK/KLF4 thus ameliorating neurovascular injury after SAH. We also revealed that ET-1/ETR is a potential therapeutic target after SAH.