Serum miR-92a-3p as a New Potential Biomarker for Diagnosis of Kawasaki Disease with Coronary Artery Lesions

Rong, Xing; Jia, Lianhong; Hong, Lanlan; Pan, Lulu; Xue, Xiangyang; Zhang, Chunxiang; Lu, Jia‐Cheng; Jin, Zengyou; Qiu, Huixian; Wu, Rongzhou; Chu, Maoping

doi:10.1007/s12265-016-9717-x

Cited by 30 publications

(29 citation statements)

References 33 publications

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“…We found in this study that serum miR‐223 had a positive correlation with blood cell (platelet and leukocyte) counts. Interestingly, miR‐92, another serum miRNA that was also increased in KD, had no correlation with platelet counts and total leukocyte counts in KD patients, as shown previously . We think the reason is that miR‐223 is a blood cell–specific miRNA, as we showed in this study and previously .…”

Section: Discussionsupporting

confidence: 62%

Bone Marrow–Derived MicroRNA‐223 Works as an Endocrine Genetic Signal in Vascular Endothelial Cells and Participates in Vascular Injury From Kawasaki Disease

Chu

Qin

et al. 2017

JAHA

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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.

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Section: Discussionsupporting

confidence: 62%

Bone Marrow–Derived MicroRNA‐223 Works as an Endocrine Genetic Signal in Vascular Endothelial Cells and Participates in Vascular Injury From Kawasaki Disease

Chu

Qin

et al. 2017

JAHA

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“…There have been a few studies that have investigated the miRNAs in KD prior to and following IVIG therapy (22,40,41). However, the roles of miR-328, miR-575, miR-134 and miR-671-5p remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Serum exosomal miR‑328, miR‑575, miR‑134 and miR‑671‑5p as potential biomarkers for the diagnosis of Kawasaki disease and the prediction of therapeutic outcomes of intravenous immunoglobulin therapy

2018

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The present study was conducted to screen serum exosomal microRNAs (miRNAs) for the early diagnosis of Kawasaki disease (KD) and to investigate their underlying mechanisms by analyzing microarray data under accession numbers GSE60965 [exosomal miRNA, including three pooled serum samples from 5 healthy children, 5 patients with KD and 5 patients with KD following intravenous immunoglobulin (IVIG) therapy] and GSE73577 (mRNA, including peripheral blood mononuclear cell samples from 19 patients with KD prior to and following IVIG treatment) from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) and genes (DEGs) were identified using the Linear Models for Microarray data method, and the mRNA targets of DE-miRNAs were predicted using the miRWalk 2.0 database. The functions of the target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). As a result, 65 DE-miRNAs were identified with different expression patterns between the healthy children and patients with KD and between patients with KD and patients with KD following IVIG therapy. The target genes of 15 common DE-miRNAs were predicted. Following overlapping the target genes of DE-miRNAs with 355 DEGs, 28 common genes were identified and further screened to construct a network containing 30 miRNA-mRNA regulatory associations. Of these associations, only miR-328-spectrin α, erythrocytic 1, miR-575-cyclic AMP-responsive element-binding protein 5/b-1,4-galactosyltransferase 5/WD repeat and FYVE domain-containing 3/cystatin-A/C-X-C motif chemokine receptor 1/protein phosphatase 1 regulatory subunit 3B, miR-134-acyl-CoA synthetase long chain family member 1/C-type lectin domain family 1 member A and miR-671-5p-tripartite motif containing 25/leucine rich repeat kinase 2/kinesin family member 1B/leucine rich repeat neuronal 1 were involved in the negative regulation of gene expression. Functional analysis indicated that the identified target genes may be associated with inflammation. Accordingly, serum exosomal miR-328, miR-575, miR-134 and miR-671-5p may act as potential biomarkers for the diagnosis of KD and the prediction of outcomes of the IVIG therapy by influencing the expression of inflammatory genes.

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“…However, none of them has been validated for clinical use. 60,61 Thus, more research is needed to identify a potential biomarker for KD that can be used in clinical practice.…”

Section: Biomarkers In Kdmentioning

confidence: 99%

Diagnosis of Kawasaki disease

2017

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Kawasaki disease (KD) is a medium vessel vasculitis with predilection for coronary arteries. Due to lack of a reliable confirmatory laboratory test, the diagnosis of KD is based on a constellation of clinical findings that appear in a typical temporal sequence. These diagnostic criteria have been modified from time to time and the most recent guidelines have been proposed by the American Heart Association (AHA) in 2017. However, several children may have incomplete or atypical forms of KD and the diagnosis can often be difficult, especially in infants and young children. In this review, we have detailed the steps involved in arriving at a diagnosis of KD and also highlight the important role of echocardiography in diagnosis and management of children with KD.

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Serum miR-92a-3p as a New Potential Biomarker for Diagnosis of Kawasaki Disease with Coronary Artery Lesions

Cited by 30 publications

References 33 publications

Bone Marrow–Derived MicroRNA‐223 Works as an Endocrine Genetic Signal in Vascular Endothelial Cells and Participates in Vascular Injury From Kawasaki Disease

Bone Marrow–Derived MicroRNA‐223 Works as an Endocrine Genetic Signal in Vascular Endothelial Cells and Participates in Vascular Injury From Kawasaki Disease

Serum exosomal miR‑328, miR‑575, miR‑134 and miR‑671‑5p as potential biomarkers for the diagnosis of Kawasaki disease and the prediction of therapeutic outcomes of intravenous immunoglobulin therapy

Diagnosis of Kawasaki disease

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