Evidence map›Paper›PMID 27923814›Full record

Trial reportCirculation research2017

miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease.

Ming He, Zhen Chen, Marcy Martin, Jin Zhang, Panjamaporn Sangwung, Brian Woo, Adriana H Tremoulet, Chisato Shimizu, Mukesh K Jain, Jane C Burns and 1 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01431105 (Phase I/IIa Study of Pharmacokinetics and Safety of Atorvastatin in Children With Coronary Artery Abnormalities Secondary to Kawasaki Disease), which is not on this map. Cited by 86 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 2 pooled it
10.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01431105 phase1 / phase2completednot on this map

Phase I/IIa Study of Pharmacokinetics and Safety of Atorvastatin in Children With Coronary Artery Abnormalities Secondary to Kawasaki Disease

TypeinterventionalSponsorUniversity of California, San DiegoRan2012 to 2018Enrolled34ConditionsKawasaki DiseaseArmsAtorvastatin
3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. miR-92a aggravates metabolic syndrome via KLF2/miR-483 axis.Journal of diabetes investigation · 2025
    Article
  15. Endothelial cell (EC)-specific Ctgf/Ccn2 expression increases EC reprogramming and atherosclerosis.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Article
  16. Article
  17. Review
  18. Review
  19. Plasma cell-free RNA signatures of inflammatory syndromes in children.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. Review

26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 2 countries.

Ming HeFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.).
Zhen ChenFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.).
Marcy MartinFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.).
Jin ZhangFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.).
Panjamaporn SangwungFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.).
Brian WooFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.).
Adriana H TremouletFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.).
Chisato ShimizuFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.).
Mukesh K JainFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.).
Jane C BurnsFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.). jshyy@ucsd.edu jcburns@ucsd.edu.
John Y-J ShyyFrom the Cardiovascular Research Center, Key Laboratory of Environment and Genes Related to Diseases (M.H., J.Z., J.Y.-J.S.), Department of Rheumatology, First Affiliated Hospital (M.H.), Xi'an Jiaotong University Health Science Center, China; Division of Cardiology, Department of Medicine (M.H., Z.C., M.M., B.W., J.Y.-J.S.) and Department of Pediatrics (A.H.T., C.S., J.C.B.), University of California, San Diego; Rady Children's Hospital, San Diego, CA (A.H.T., J.C.B.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); and Case Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cardiovascular Research Center, Cleveland, OH (P.S., M.K.J.). jshyy@ucsd.edu jcburns@ucsd.edu.
University of California, Riverside · US

Funding

Training In Cardiovascular Physiology & PharmacologyT32HL007444 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Ju Chen, Robert Scott Ross · 1985 to 2026
$11.1M
Shear Regulation of MicroRNA Transportomes and Targetomes in Vascular HomeostasisR01HL106579 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2011 to 2022
$8.3M
Flow-Induced Endothelial Innate Immunity and Atherosclerosis SusceptibilityR01HL125643 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHYY, JOHN YJ · 2016 to 2019
$1.7M
Phase I and IIa trial of atorvastatin in children with acute Kawasaki diseaseR01HD081296 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREMOULET, ADRIANA H · 2014 to 2017
$1.3M
Hypoxia-Suppressed Dicer and AGO1 Promote AngiogenesisR00HL122368 · NHLBI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, ZHEN BOUMAN · 2017 to 2019
$747k
Hypoxia-Suppressed Dicer and AGO1 Promote AngiogenesisK99HL122368 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, ZHEN BOUMAN · 2014 to 2015
$268k
NHLBI NIH HHS K99 HL122368NHLBI NIH HHS R00 HL122368NHLBI NIH HHS R01 HL106579NHLBI NIH HHS R01 HL125643NHLBI NIH HHS T32 HL007444NICHD NIH HHS R01 HD081296
6 · The paper itself

Abstract

rationaleEndothelial-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD.

objectiveWe investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis. As well, the modulation of this process by statin therapy was studied. METHODS AND

resultsSera from healthy children and KD subjects were incubated with human umbilical vein endothelial cells. Cardiovascular disease-related miRNAs, CTGF, and EndoMT markers were quantified using reverse transcriptase quantitative polymerase chain reaction, ELISA, and Western blotting. Compared with healthy controls, human umbilical vein endothelial cell incubated with sera from acute KD patients had decreased miR-483, increased CTGF, and increased EndoMT markers. Bioinformatics analysis followed by functional validation demonstrated that Krüppel-like factor 4 (KLF4) transactivates miR-483, which in turn targets the 3' untranslated region of CTGF mRNA. Overexpression of KLF4 or pre-miR-483 suppressed, whereas knockdown of KLF4 or anti-miR-483 enhanced, CTGF expression in endothelial cells in vitro and in vivo. Furthermore, atorvastatin, currently being tested in a phase I/IIa clinical trial in KD children, induced KLF4-miR-483, which suppressed CTGF and EndoMT in endothelial cells.

conclusionsKD sera suppress the KLF4-miR-483 axis in endothelial cells, leading to increased expression of CTGF and induction of EndoMT. This detrimental process in the endothelium may contribute to coronary artery abnormalities in KD patients. Statin therapy may benefit acute KD patients, in part, through the restoration of KLF4-miR-483 expression. CLINICAL

trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01431105.

Indexed as

AnimalsAtorvastatinCattleChild, PreschoolConnective Tissue Growth FactorDose-Response Relationship, DrugEndothelial CellsEpithelial-Mesenchymal TransitionFemaleGene TargetingHumansHuman Umbilical Vein Endothelial CellsHydroxymethylglutaryl-CoA Reductase InhibitorsInfantKruppel-Like Factor 4MaleAtorvastatinCCN2 protein, humanConnective Tissue Growth FactorHydroxymethylglutaryl-CoA Reductase InhibitorsKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4MicroRNAsMIRN483 microRNA, humanatorvastatinCTGFEndoMTendothelial dysfunctionKawasaki diseasemicroRNAmiR-483

Identifiers

PMID27923814
PMCPMC5391835
OpenAlexW2560259033

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.