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Background: Mitral chordae tendineae rupture (MCTR) is a progressive disorder which leads to severe mitral regurgitation. Despite its importance, the precise pathogenetic mechanism of MCTR remains unclear. The study aim was to investigate the expression profile of circulating microRNAs (miRNAs) as being potentially involved in the development of MCTR., Methods: Twenty-one patients with 'primary' MCTR, and 30 age- and gender-matched controls, were enrolled in the study. Comparisons were made between the expression levels of circulating miRNAs in MCTR patients and controls. Four target gene databases were used to predict target genes and pathways of differentially expressed miRNAs., Results: Compared to controls, the expression of 22 miRNAs (hsa-miR-106b-5p, hsa-miR-126-3p, hsa-miR-150-5p, hsa-miR-17-5p, hsa-miR-195-5p, hsa-miR-19a-3p, hsa-miR-19b-3p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-222-3p, hsa-miR-223-3p, hsa-miR-23a-3p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-93-5p, hsa-miR-26b-5p, hsa-miR-30e-5p, hsa-miR-373-3p, hsa-miR-15b-5p, hsa-miR-16-5p, hsa-miR-191-5p, hsa-miR-26a-5p) were significantly down-regulated in the MCTR group. Bioinformatic analysis indicated that the following potential miRNA targets and pathways are commonly related to the development of MCTR: MMPs, TIMP-2,TGFBR2, VEGFA, PIK3R2, NRAS, PPP3CA, PPP3R1, PTGS 2 were predicted as putative targets of 13 of these miRNAs., Conclusions: The present study is the first to describe altered miRNA expression in patients with MCTR. Bioinformatic analysis has revealed that target genes involved in MCTR development were regulated by miRNAs.