Department of Marine Biomedicine and Polar Medicine, Naval Medical University (Second Military Medical University), Shanghai, 200433, China.
School of Basic Medical Sciences, Naval Medical University (Second Military Medical University), Shanghai, 200433, China.
J Cardiovasc Transl Res. 2022 Jun;15(3):500-513. doi: 10.1007/s12265-022-10266-5. Epub 2022 May 2.
Sympathetic hyperactivity plays an important role in the progression of chronic heart failure (CHF). It is reported that inflammation in the rostral ventrolateral medulla (RVLM), a key region for sympathetic control, excites the activity of neurons and leads to an increase in sympathetic outflow. Exosome, as the carrier of microRNAs (miRNAs), has the function of crossing the blood-brain barrier. The present study was designed to investigate the effect of exosomal miRNAs on central inflammation via peripheral-central interaction in CHF. The miRNA microarray detection was performed to compare the difference between circulating exosomes and the RVLM in CHF rats. It was shown that the expression of miR-214-3p was significantly up-regulated, whereas let-7g-5p and let-7i-5p were significantly down-regulated in circulating exosomes and the RVLM. Further studies in PC12 cells revealed that miR-214-3p enhanced the inflammatory response, while let-7g-5p and let-7i-5p reduced the neuroinflammation. The direct interaction between the miRNA and its inflammatory target gene (miR-214-3p, Traf3; let-7g-5p, Smad2; and let-7i-5p, Mapk6) was confirmed by the dual-luciferase reporter assay. These results suggest that the circulating exosomes participate in the enhancement of inflammatory response in the RVLM through their packaged miRNAs, which may further contribute to sympathetic hyperactivity in CHF.
交感神经过度活跃在慢性心力衰竭（CHF）的进展中起着重要作用。据报道，延髓头端腹外侧区（RVLM）的炎症是交感控制的关键区域，它兴奋神经元的活性，导致交感传出增加。外泌体作为 microRNAs（miRNAs）的载体，具有穿过血脑屏障的功能。本研究旨在通过外周-中枢相互作用探讨 CHF 中外周来源的 exosomal miRNAs 对中枢炎症的影响。通过 miRNA 微阵列检测比较 CHF 大鼠循环 exosomes 和 RVLM 之间的差异。结果表明，循环 exosomes 和 RVLM 中 miR-214-3p 的表达明显上调，而 let-7g-5p 和 let-7i-5p 的表达明显下调。进一步在 PC12 细胞中的研究表明，miR-214-3p 增强了炎症反应，而 let-7g-5p 和 let-7i-5p 减轻了神经炎症。miRNA 与其炎症靶基因（miR-214-3p、Traf3；let-7g-5p、Smad2；和 let-7i-5p、Mapk6）之间的直接相互作用通过双荧光素酶报告基因检测得到证实。这些结果表明，循环 exosomes 通过其包裹的 miRNAs 参与 RVLM 中炎症反应的增强，这可能进一步导致 CHF 中的交感神经过度活跃。
