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Abstract：
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.
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 upregulation.
CONCLUSIONS: miR-193b-3p and miR-346 are newly identified factors in RVLM that hinder hypertension progression, and the miR-193b-3p/Arhgef9/apoptosis pathway presents a potential mechanism, highlighting the potential of targeting miRNAs for hypertension prevention.
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 upregulation.
CONCLUSIONS: miR-193b-3p and miR-346 are newly identified factors in RVLM that hinder hypertension progression, and the miR-193b-3p/Arhgef9/apoptosis pathway presents a potential mechanism, highlighting the potential of targeting miRNAs for hypertension prevention.
摘要：
背景：延髓腹外侧（RVLM）神经元过度活跃会引起交感神经流出，导致高血压。microRNAs（miRNAs）有助于不同的生物过程，但是它们对RVLM神经元兴奋性和血压（BP）的影响仍未被广泛研究。
结果：使用RNA测序揭示了自发性高血压大鼠的RVLMmiRNA谱。通过各种实验研究了这些miRNA在降低神经元兴奋性和BP中的潜在作用以及潜在机制。鉴定出六百三十七个miRNAs，在自发性高血压大鼠的RVLM中观察到miR-193b-3p和miR-346的水平降低。RVLM中miR-193b-3p和miR-346表达的增加降低了神经元兴奋性，同情流出，自发性高血压大鼠的血压。相比之下,抑制miR-193b-3p和miR-346在RVLM中的表达增加神经元兴奋性，同情流出，和BP在WistarKyoto和Sprague-Dawley大鼠中。Cdc42鸟嘌呤核苷酸交换因子(Arhgef9)被公认为miR-193b-3p的靶标。过表达miR-193b-3p导致Arhgef9表达明显降低，导致神经元凋亡的抑制。相比之下,它的下调产生了相反的效果。重要的是,神经元兴奋性的降低，同情流出，在自发性高血压大鼠中由于miR-193b-3p过表达而观察到的BP被Arhgef9上调大大抵消。
结论：miR-193b-3p和miR-346是RVLM中新发现的阻碍高血压进展的因子，miR-193b-3p/Arhgef9/细胞凋亡通路呈现潜在的机制,强调靶向miRNA预防高血压的潜力。
结果：使用RNA测序揭示了自发性高血压大鼠的RVLMmiRNA谱。通过各种实验研究了这些miRNA在降低神经元兴奋性和BP中的潜在作用以及潜在机制。鉴定出六百三十七个miRNAs，在自发性高血压大鼠的RVLM中观察到miR-193b-3p和miR-346的水平降低。RVLM中miR-193b-3p和miR-346表达的增加降低了神经元兴奋性，同情流出，自发性高血压大鼠的血压。相比之下,抑制miR-193b-3p和miR-346在RVLM中的表达增加神经元兴奋性，同情流出，和BP在WistarKyoto和Sprague-Dawley大鼠中。Cdc42鸟嘌呤核苷酸交换因子(Arhgef9)被公认为miR-193b-3p的靶标。过表达miR-193b-3p导致Arhgef9表达明显降低，导致神经元凋亡的抑制。相比之下,它的下调产生了相反的效果。重要的是,神经元兴奋性的降低，同情流出，在自发性高血压大鼠中由于miR-193b-3p过表达而观察到的BP被Arhgef9上调大大抵消。
结论：miR-193b-3p和miR-346是RVLM中新发现的阻碍高血压进展的因子，miR-193b-3p/Arhgef9/细胞凋亡通路呈现潜在的机制,强调靶向miRNA预防高血压的潜力。
