Abstract 137: Vascular Smooth Muscle Cell MYPT1 Deficiency Induces Phenotype Switching and Disrupts Blood-Brain Barrier After Stroke

Objectives: Cerebral autoregulation and blood brain barrier (BBB) are often impaired in hypertensive and aging individuals, contributing to the development of stroke. Vascular smooth muscle cells (VSMC) play a vital role in cerebral blood flow control and maintenance of BBB. Ischemic injury triggers VSMC to switch into a detrimental phenotype in peripheral blood vessels, however, the pathological phenotype switching in cerebral VSMC and the impact of VSMC on BBB are not elucidated thoroughly in stroke with hypertension. Methods: Hypertensive mice with smooth muscle–specific deletion of MYPT1 (MYPT1 SMKO mice) were generated. Middle cerebral artery occlusion (MCAO) was conducted in adult MYPT1 SMKO mice and their wild-type (WT) mice for 60 min. Ischemic infarct volumes and neurological function were evaluated. Evens blue, immunofluorescence (IF), western blot (WB) and so on were performed to evaluate the permeability of BBB after stroke. The phenotype switching of VSMC was measured by WB, IF and quantitative real-time polymerase chain reaction (q-PCR) in oxygen glucose deprivation (OGD) and co-cultured in vitro models. Proteomic analysis was performed in cerebral capillaries. The q-PCR and WB were used for further validation. Results: It was found that the infarct volumes and neurological deficits were aggravated in MYPT1 SMKO mice and the permeability of BBB was increased. The loss of pericyte cells and degradation of basement membrane of BBB were more severe in MYPT1 SMKO mice. Furthermore, the protein expression of α-SMA in MYPT1 SMKO mice after MCAO was reduced and the protein expression of Calponin and SM-22α was reduced. The ability of migration and proliferation in VSMC of MYPT1-knockout was altered after OGD. Proteomic analysis showed that the expression of protein associated with inflammation in VSMC of MYPT1 SMKO mice was increased than that of WT mice, but the specific protein underlying the mechanism needs further verification. Conclusions: The damage of BBB was increased in MYPT1 SMKO hypertensive mice. And there is a phenotype switching in cerebral VSMC after stroke in MYPT1 SMKO hypertensive mice. The potential mechanism may involve the increasing expression of protein associated with inflammation in VSMC that needs further verification.