The Peripheral Circulating Exosomal microRNAs Related to Central Inflammation in Chronic Heart Failure

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.