miR‐193b‐3p and miR‐346 Exert Antihypertensive Effects in the Rostral Ventrolateral Medulla

作者：Shuai Zhang, Xueping Wang, Tengteng Dai, Lei Tong, Gaojun Chen, Linping Wang, Zhangyan Ren, Haisheng Liu, Dongshu Du · 发表于：Journal of the American Heart Association · 年份：2024 · DOI：10.1161/jaha.124.034965 · 被引用次数：7 · 研究领域：MicroRNA in disease regulation、Cardiovascular, Neuropeptides, and Oxidative Stress Research、Circular RNAs in diseases

Background Rostral ventrolateral medulla (RVLM) neuron hyperactivity raises sympathetic outflow, causing hypertension. MicroRNAs (miRNAs) contribute to diverse biological processes, but their influence on RVLM neuronal excitability and blood pressure (BP) remains widely unexplored. Methods and Results The RVLM miRNA profiles in spontaneously hypertensive rats were unveiled using RNA sequencing. Potential effects of these miRNAs in reducing neuronal excitability and BP and underlying mechanisms were investigated through various experiments. Six hundred thirty‐seven miRNAs were identified, and reduced levels of miR‐193b‐3p and miR‐346 were observed in the RVLM of spontaneously hypertensive rats. Increased miR‐193b‐3p and miR‐346 expression in RVLM lowered neuronal excitability, sympathetic outflow, and BP in spontaneously hypertensive rats. In contrast, suppressing miR‐193b‐3p and miR‐346 expression in RVLM increased neuronal excitability, sympathetic outflow, and BP in Wistar Kyoto and Sprague‐Dawley rats. Cdc42 guanine nucleotide exchange factor ( Arhgef9) was recognized as a target of miR‐193b‐3p. Overexpressing miR‐193b‐3p caused an evident decrease in Arhgef9 expression, resulting in the inhibition of neuronal apoptosis. By contrast, its downregulation produced the opposite effects. Importantly, the decrease in neuronal excitability, sympathetic outflow, and BP observed in spontaneously hypertensive rats due to miR‐193b‐3p overexpression was greatly counteracted by Arhgef9...