Suppression of macrophage enriched miRNA 210-3p improves cardiac fibrosis and cardiac function following myocardial infarction.

Abstract

BackgroundAlthough it is well-known that immune cells such as monocytes or macrophages play important roles during the early phase of inflammatory response following cardiac damage, little is known about the role of immune cell-derived exosomes, especially their contents such as micro RNAs (miRNAs), in the immune cell-mediated regulation of cardiac remodeling. This study investigated the role of macrophage-derived exosomal miR-210-3p, which was found to be increased following cardiac damage, on cardiac fibroblast activation using a rat myocardial infarction (MI) model.MethodsCell population change in the heart following MI was assessed by single cell analysis. Differentially expressed miRNAs in the exosomes derived from THP-1 cultured under hypoxia/ischemia condition was evaluated by miRNA sequencing. The effect of macrophage exosome enriched miR-210-3p on cardiac fibroblast was examined. The effect of anti-miR-210-3p administration on the MI-induced cardiac fibrosis, cardiac function, and macrophage infiltration were evaluated.ResultsMacrophages were identified as the major type of immune cells present in the ischemic tissue following MI. miR-210a-3p was one of the 10 miRNAs increased (>10-fold) in THP-1 in response to hypoxia/ischemia condition, and it exerted pro-fibrotic effect in cardiac fibroblasts. Conditioned media of THP-1 cultured under hypoxia/ischemia condition also activated cardiac fibroblasts, and this was abrogated by anti-miR-210 treatment. Intramuscular injection of anti-miR-210-3p improved cardiac fibrosis and cardiac function 14 day after MI.ConclusionsMacrophage derived exosomes were enriched with miR-210-3p under hypoxia/ischemic condition, and they activated cardiac fibroblast. Suppression of miR-210-3p improved cardiac fibrosis and cardiac function following MI. Macrophage-derived exosomal miR-210-3p may play a significant role in the regulation of early inflammatory response following cardiac injury.