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BackgroundKawasaki disease (KD) is now the most common cause of acquired cardiac disease in children due to permanent coronary artery damage with unknown etiology. The study sought to determine the role of blood microRNA miR‐223 in KD and KD‐induced injuries in vascular endothelial cells (ECs) as well as the mechanisms involved.Methods and ResultsMicroRNA profiles in serum from patients with KD and from healthy controls were assessed by microarray analysis. We noted that multiple serum microRNAs were aberrantly expressed in KD, among them miR‐223, which was the most upregulated abundant serum microRNA. We found that bone marrow–derived blood cells (leukocytes and platelets) were able to secrete miR‐223 into serum. Vascular ECs had no endogenous miR‐223; however, the blood cell–secreted serum miR‐223 could enter into the vascular ECs in the vascular walls. The exogenous miR‐223 had strong biological effects on EC functions via its target genes such as IGF1R. Interestingly, KD‐induced EC injuries were related to increased miR‐223 because they were inhibited by miR‐223 knockdown. Finally, these observations were verified using miR‐223 knockout mice and the chimeric mice generated by transplantation of bone marrow from miR‐223 knockout mice into wild‐type mice.ConclusionsIn KD patients, the levels of blood cell–derived miR‐223 in ECs are significantly increased. The increased miR‐223 in ECs could work as a novel endocrine genetic signal and participate in vascular injury of KD. MiR‐223 may provide a novel mechanism and a new therapeutic target for vascular complication of KD.

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.

Recent studies have suggested that serum microRNAs (miRNAs) are novel biomarkers for many cardiovascular diseases, but their role in Kawasaki disease (KD) is still unclear. We demonstrated that serum miR-92a-3p levels were significantly higher in children with KD compared with children with fever and controls (both P < 0.05). When the disease recovered, miR-92a-3p levels returned to those of controls. Clinical and pathological data showed that high levels of miR-92a-3p were significantly associated with coronary artery lesions (CALs). Analysis of the receiver operating characteristic (ROC) curve showed that serum miR-92a-3p had a sensitivity of 81.8% and a specificity of 66.7% for distinguishing KD with CALs from KD without CALs. The area under the curve was 0.816 (P < 0.05, 95% CI 0.669-0.962). Therefore, the miRNA miR-92a-3p may be used as a potential biomarker for diagnosis of KD and KD with coronary artery lesions.