Minyue Jia, Liya Lin, Boyun Yang, Hanxiao Yu, Shan Zhong, Xiaohong Xu, Xiaoxiao Song
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引用次数: 0
Abstract
Inappropriate aldosterone production relative to sodium status is known to induce arterial hypertension and cause detrimental effects on endothelium and vascular remodeling. This study investigated whether microRNAs (miRs) serve as key mediators of aldosterone's effects on endothelial dysfunction. Using human umbilical vein endothelial cells (HUVECs) as a model system, we demonstrated that aldosterone treatment suppressed cellular proliferation and migration while promoting senescence. Mechanistically, we observed that aldosterone exposure significantly upregulated miR-34a expression in HUVECs. The functional significance of miR-34a was confirmed when specific inhibitors reversed aldosterone's antiproliferative and prosenescence effects. To elucidate the underlying molecular pathway, we performed comprehensive biological analyses, which revealed that miR-34a target genes were predominantly associated with the Notch signaling pathway. Western blot analysis further validated that miR-34a promotes senescence in HUVECs through negative regulation of NOTCH1. Collectively, our findings identify miR-34a as a crucial mediator of aldosterone-induced endothelial cell senescence via the NOTCH1 signaling pathway, suggesting its potential as a therapeutic target for aldosterone-related vascular diseases.
期刊介绍:
International Journal of Hypertension is a peer-reviewed, Open Access journal that provides a forum for clinicians and basic scientists interested in blood pressure regulation and pathophysiology, as well as treatment and prevention of hypertension. The journal publishes original research articles, review articles, and clinical studies on the etiology and risk factors of hypertension, with a special focus on vascular biology, epidemiology, pediatric hypertension, and hypertensive nephropathy.