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Atrial fibrosis is a crucial contributor to initiation and perpetuation of atrial fibrillation (AF). This study aimed to identify a circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory network related to atrial fibrosis in AF, especially to validate hsa_circ_0000672/hsa_miR-516a-5p/TRAF6 ceRNA axis in AF preliminarily. The circRNA-miRNA-mRNA ceRNA network associated with AF fibrosis was constructed using bioinformatic tools and literature reviews. Left atrium (LA) low voltage was used to represent LA fibrosis by using LA voltage matrix mapping. Ten controls with sinus rhythm (SR), and 20 patients with persistent AF including 12 patients with LA low voltage and 8 patients with LA normal voltage were enrolled in this study. The ceRNA regulatory network associated with atrial fibrosis was successfully constructed, which included up-regulated hsa_circ_0000672 and hsa_circ_0003916, down-regulated miR-516a-5p and five up-regulated hub genes (KRAS, SMAD2, TRAF6, MAPK11 and SMURF1). In addition, according to the results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, these hub genes were clustered in TGF-beta and MAPK signaling pathway. In the patients with persistent AF, hsa_circ_0000672 expression in peripheral blood monocytes was significantly higher than those in controls with SR by quantitative real-time polymerase chain reaction (p-value < 0.001). Furthermore, hsa_circ_0000672 expression was higher in peripheral blood monocytes of persistent AF patients with LA low voltage than those with LA normal voltage (p-value = 0.002). The dual-luciferase activity assay confirmed that hsa_circ_0000672 exerted biological functions as a sponge of miR-516a-5p to regulate expression of its target gene TRAF6. Hsa_circ_0000672 expression in peripheral blood monocytes may be associated with atrial fibrosis. The hsa_circ_0000672 may be involved in atrial fibrosis by indirectly regulating TRAF6 as a ceRNA by sponging miR-516a-5p. [ABSTRACT FROM AUTHOR]

Coronary microembolization (CME) is a spontaneous event in patients with ischemic heart disease and a potential iatrogenic complication in patients undergoing coronary interventions. CME induces an obvious inflammatory reaction, characterized by cellular infiltration, particularly of eosinophils, and multifocal microinfarcts. However, little is known on the correlation between pro- and anti-inflammatory cytokines and cardiac function following CME. In this study, microspheres with a diameter of 42 μm were intracoronarily injected into the apex of the left ventricle to induce CME (CME group). Rats injected with normal saline served as controls (sham operated control group). Expression of pro-inflammatory cytokines, TNF-α and IL-1β, and an anti-inflammatory cytokine, IL-10, was measured at 3, 6, 12, 24 h, and 4 weeks post-injection by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. At the same time points, cardiac function and histological changes were evaluated by echocardiographic imagining and H&E staining, respectively. It was observed that the mRNA and protein expressions of TNF-α, IL-1β, and IL-10 all started to increase at 3 h, reached to the peak levels at 12 h, and returned to the normal levels at 4 weeks post-injection. The left ventricular ejection fraction (LVEF) was significantly lower in the CME group than in the control group at 3, 6, 12, 24 h, and 4 weeks post-injection. Obvious myocardial microinfarcts with surrounding myocardial edema and degeneration, caryolysis, and infiltration of neutrophils and monocytes were observed in the CME group at 3, 6, 12, 24 h, and 4 weeks post-injection. Moreover, mRNA expression of TNF-α and IL-1β was negatively correlated with LVEF, although not with myocardial microinfarcts, in the CME group. It is concluded that both protein and mRNA expression of TNF-α IL-1β and IL-10 are dynamically changed following CME, which is associated with reduced cardiac function. Therefore, these cytokines may be potential therapeutic targets for clinical treatment of CME. [ABSTRACT FROM AUTHOR]