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- W3174230833 abstract "Enhanced activation of mineralocorticoid receptors (MRs) impairs insulin metabolic signaling, increases oxidative stress, and induces inflammation with associated cardiovascular abnormalities. Our previous data in female mice suggests that activation of endothelial cell MRs (ECMR) contributes to development of vascular stiffness partly by impairing insulin metabolic signaling and reducing endothelial derived nitic oxide (NO) production. Emerging information suggests that microRNA 103 (miR103) is upregulated and thus promotes endothelial inflammation and atherosclerosis in both ob/ob mice and western diet-induced obese C57BL/6J mice. However, the interaction of ECMR and miR103 in the promotion of vascular inflammation and stiffness has not been explored. We hypothesized that ECMR signaling prompts vascular inflammation and stiffness through miRNA-103-mediated suppression of Kruppel-like factor-4 (KLF4). Female ECMR knockout (ECMR -/- ) and wild-type littermate females were treated with aldosterone (Aldo) (250 μg/kg/day) via osmotic minipumps for 4 weeks. Aldo infusion induced endothelium stiffness and impaired aortic relaxation in wild-type mice as determined by ex vivo atomic force microscopy and wire myograph techniques, respectively. The elevated aortic stiffness and impaired relaxation was accompanied by increases in expression of miR103 and intercellular adhesion molecule 1 (ICAM-1) and a reduction in phosphorylation of serine (Ser) 1177/activation of endothelial NO synthase (eNOS). These Aldo-induced endothelial abnormalities were prevented in ECMR -/- mice. Furthermore, application of a miR103 inhibitor to ECs in vitro attenuated Aldo (10 8 M)-induced a decrease in KLF4 expression, which has anti-inflammatory functions mediated by upregulation of phosphorylation of eNOS and downregulation of ICAM-1. These findings suggest that increased ECMR signaling and associated miR103 activation plays a key role in Aldo-induced KLF4 suppression and associated vascular inflammation and aortic stiffness in females." @default.
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- W3174230833 date "2016-09-01" @default.
- W3174230833 modified "2023-09-23" @default.
- W3174230833 title "Abstract 127: Enhanced Endothelial Mineralocorticoid Receptor Signaling Prompts Vascular Inflammation and Stiffness Through MiRNA-103-mediated Suppression of KLF4" @default.
- W3174230833 doi "https://doi.org/10.1161/hyp.68.suppl_1.127" @default.
- W3174230833 hasPublicationYear "2016" @default.
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