Kawasaki disease (KD) is an acute, self-limited vasculitis that predominantly affects medium-sized arteries, particularly the coronary arteries. Recent studies have indicated that microRNAs are involved in many diseases, including KD. However, the detailed mechanism remains unclear. The aim of the present study was to explore the role of miR-186 in KD and potentially discover a new target for KD treatment. The results demonstrated that miR-186 was upregulated in serum from patients with KD and KD serum could increase miR-186 transcript levels in endothelial cells (HUVECs). Overexpression of miR-186 mimic induced HUVEC apoptosis through mitogen-activated protein kinase (MAPK) activation by targeting and inhibiting SMAD family member 6 (SMAD6). Furthermore, KD serum induced HUVEC apoptosis through miR-186. In conclusion, the present results suggested that KD serum-associated miR-186 has an essential role in endothelial cell apoptosis by activating the MAPK pathway through targeting the SMAD6 gene.

Induced pluripotent stem cell‐derived conditioned medium ( iPS ‐ CM ) could improve cell viability in many types of cells and may be a better alternative for the treatment of myocardial infarction. This study aimed to examine the influence of iPS ‐ CM on anti‐apoptosis and the proliferation of H9C2 cardiomyocytes and investigate the underlying mechanisms. H9C2 cardiomyocytes were exposed to 200 μmol/L hydrogen peroxide (H 2 O 2 ) for 24 hours with or without pre‐treatment with iPS ‐ CM . The ratio of apoptotic cells, the loss of mitochondrial membrane potential (△Ψm) and the levels of intracellular reactive oxygen species were analysed by flow cytometric analysis. The expression levels of BCL ‐2 and BAX proteins were analysed by Western blot. Cell proliferation was assessed using cell cycle and EdU staining assays. To study cell senescence, senescence‐associated β‐galactosidase ( SA ‐β‐gal) staining was conducted. The levels of malondialdehyde, superoxide dismutase and glutathione were also quantified using commercially available enzymatic kits. The results showed that iPS ‐ CM containing basic fibroblast growth factor significantly reduced H 2 O 2 ‐induced H9C2 cardiomyocyte apoptosis by activating the autophagy flux pathway, promoted cardiomyocyte proliferation by up‐regulating the Wnt/β‐catenin pathway and inhibited oxidative stress and cell senescence. In conclusion, iPS ‐ CM effectively enhanced the cell viability of H9C2 cardiomyocytes and could potentially be used to inhibit cardiomyocytes apoptosis to treat myocardial infarction in the future.

A20, a negative regulator of nuclear factor κB signaling, has been shown to attenuate atherosclerotic events. Transforming growth factor beta-activated kinase 1 (TAK1) plays a critical role in TNFα-induced atherosclerosis via endothelial nitric oxide (NO) synthase (eNOS) uncoupling and NO reduction. In the study, we investigated the hypothesis that A20 protected endothelial cell injury induced by TNFα through modulating eNOS activity and TAK1 signalling. Human umbilical vein endothelial cells (HUVECs) were stimulated by TNFα. The impact of A20 on cell apoptosis, eNOS expression and NO production and related TAK1 pathway were detected. Both eNOS and NO production were remarkably reduced. TAK1, p38 MAPK phosphorylation and HUVECs apoptosis were enhanced after TNFα stimulation for 2 hrs. Inhibition of A20 significantly activated TAK1, p38 MAPK phosphorylation, and cell apoptosis, but blocked eNOS expression and NO production. Furthermore, p38 MAPK expression was suppressed by A20 over-expression, but re-enhanced by inhibiting A20 or activation of TAK1. Furtherly, TNFα-induced suppression of eNOS and NO production were largely prevented by silencing p38 MAPK. Collectively, our results suggested that A20-mediated TAK1 inactivation suppresses p38 MAPK and regulated MAPK/eNOS pathway, which contributes to endothelial cell survival and function preservation.