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A Single-Short Partial Reprogramming of the Endothelial Cells decreases Blood Pressure via attenuation of EndMT in Hypertensive Mice

ABSTRACT: Small artery remodeling and endothelial dysfunction are hallmarks of hypertension. Evidence supports a likely causal association between cardiovascular diseases and endothelial-to-mesenchymal transition (EndMT), a cellular transdifferentiation process in which endothelial cells (ECs) partially lose their identity and acquire mesenchymal phenotypes. EC reprogramming represents an innovative strategy in regenerative medicine to prevent deleterious effects induced by cardiovascular diseases. We hypothesized that arteries from hypertensive mice present high levels of EndMT and that specific EC reprogramming can decrease blood pressure values and restore vascular function in resistance arteries in hypertensive mice. Here, we demonstrated OSK overexpression induced partial EC reprogramming in vitro, and these cells had lower migratory capability. Using spatial whole transcriptome atlas, we showed that OSK treatment of hypertensive BPH/2J mice attenuated EndMT and elastin breaks, and by other assays, we showed that OSK treatment reduced blood pressure and resistance arteries hypercontractility. OSK-treated hypertensive HAoECs showed high eNOS activation and NO production, with low ROS formation. Single-cell RNA analysis showed that OSK alleviated EC senescence and EndMT, restoring their phenotypes in HAoECs from hypertensive patients. Overall, these data indicate that OSK treatment and EC reprogramming can decrease blood pressure and reverse hypertension-induced vascular damage.

ORGANISM(S): Mus musculus

PROVIDER: GSE298954 | GEO | 2025/08/26

REPOSITORIES: GEO

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A Single-Short Partial Reprogramming of the Endothelial Cells decreases Blood Pressure via attenuation of EndMT in Hypertensive Mice

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