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• W4386509895 endingPage "111162" @default.
• W4386509895 startingPage "111162" @default.
• W4386509895 abstract "The major pathophysiological characteristic of hypertension is the occurrence of small artery remodeling and endothelial dysfunction. There is also solid evidence showing that microcirculation abnormalities occur prior to the onset of hypertension. However, the mechanism(s) that trigger these changes prior to the elevation of blood pressure are unknown, and this may limit our ability to identify the cause of this disease and effectively treat it. In hypertension, as with aging, the vasculature becomes less susceptible to repair. One of the reasons is because endothelial cells start to deteriorate and present with exacerbated endothelial-to-mesenchymal transition (EndMT). Likewise, vascular smooth muscle cells (VSMC) also dedifferentiate into a synthetic phenotype, whereby they start to produce and secrete extracellular vesicles with a high migration and proliferation capacity for repairing vascular injury. Uncontrolled EndMT and/or VSMC phenotype switching contributes to vascular diseases, but the initial trigger for these conditions is unidentified. Importantly, EndMT and synthetic VSMC exhibit plasticity and can return to adopt an endothelial cell-like fate and present contractile phenotype again, respectively. Therefore, in this hypothesis we will take advantage of this plasticity, and we propose to manipulate this fate by inducing partial cellular reprogramming without passing through the pluripotent state. Specifically, we suggest that activation of the three master transcription factors, Oct-4, Sox-2, and Klf-4 (collectively termed OSK) will reprogram endothelial cells and prevent and reduce EndMT and VSMC synthetic phenotype. It was recently shown that activation of OSK was able to restore lost vision in old mice, and cancer risk was reduced by excluding c-Myc. Therefore, OSK treatment could provide new possibilities for vascular rejuvenation and treatment of hypertension." @default.
• W4386509895 created "2023-09-08" @default.
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• W4386509895 date "2023-10-01" @default.
• W4386509895 modified "2023-10-17" @default.
• W4386509895 title "Reprogramming endothelial and vascular smooth muscle cells to prevent and treat hypertension" @default.
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• W4386509895 doi "https://doi.org/10.1016/j.mehy.2023.111162" @default.
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