Go to JCI Insight
Jci spelled out white on transparent.20160208
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Biology of familial cancer predisposition syndromes (Feb 2019)
    • Mitochondrial dysfunction in disease (Aug 2018)
    • Lipid mediators of disease (Jul 2018)
    • Cellular senescence in human disease (Apr 2018)
    • Fibrosis (Jan 2018)
    • Glia and Neurodegeneration (Sep 2017)
    • Transplantation (Jun 2017)
    • View all review series...
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Scientific Show Stoppers
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

Jci only white

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication
Top
  • View PDF Adobe pdf file icon
  • Download citation information
  • Send a letter
  • License information
  • Standard abbreviations
  • Article usage
  • Citations to this article
  • Share this article
  • Need Help? E-mail the JCI
  • Top
  • Abstract
  • Supplemental material
  • Version history
Advertisement

ResearchIn-Press PreviewVascular biology Free access | 10.1172/JCI124508

Platelet-derived miR-223 promotes a phenotypic switch in arterial injury repair

Zhi Zeng, Luoxing Xia, Xuejiao Fan, Allison C. Ostriker, Timur Yarovinsky, Meiling Su, Yuan Zhang, Xiangwen Peng, Xie Yi, Lei Pi, Xiaoqiong Gu, Sookja Kim Chung, Kathleen A. Martin, Renjing Liu, John Hwa, and Wai Ho Tang

Find articles by Zeng, Z. in: JCI | PubMed | Google Scholar

Find articles by Xia, L. in: JCI | PubMed | Google Scholar

Find articles by Fan, X. in: JCI | PubMed | Google Scholar

Find articles by Ostriker, A. in: JCI | PubMed | Google Scholar

Find articles by Yarovinsky, T. in: JCI | PubMed | Google Scholar | Orcid 24x24

Find articles by Su, M. in: JCI | PubMed | Google Scholar

Find articles by Zhang, Y. in: JCI | PubMed | Google Scholar

Find articles by Peng, X. in: JCI | PubMed | Google Scholar

Find articles by Yi, X. in: JCI | PubMed | Google Scholar | Orcid 24x24

Find articles by Pi, L. in: JCI | PubMed | Google Scholar

Find articles by Gu, X. in: JCI | PubMed | Google Scholar

Find articles by Chung, S. in: JCI | PubMed | Google Scholar

Find articles by Martin, K. in: JCI | PubMed | Google Scholar

Find articles by Liu, R. in: JCI | PubMed | Google Scholar

Find articles by Hwa, J. in: JCI | PubMed | Google Scholar

Find articles by Tang, W. in: JCI | PubMed | Google Scholar

First published January 15, 2019 - More info

J Clin Invest. https://doi.org/10.1172/JCI124508.
Copyright © 2019, American Society for Clinical Investigation

First published January 15, 2019 - Version history
Abstract

Upon arterial injury, endothelial denudation leads to platelet activation, and delivery of multiple agents (e.g. TXA2, PDGF) promoting VSMC dedifferentiation, and proliferation, in injury repair (intimal hyperplasia). Resolution of vessel injury repair, and prevention of excessive repair (switching VSMC back to a differentiated quiescent state) is a poorly understood process. We now report that internalization of activated platelets by VSMCs promotes resolution of arterial injury by switching on VSMC quiescence. Ex vivo and in vivo studies using lineage tracing reporter mice (PF4-Cre x mTmG) demonstrated uptake of green platelets by red vascular smooth muscle cells upon arterial wire injury. Genome-wide miRNA sequencing of VSMCs co-cultured with activated platelets identified significant increases in platelet-derived miR-223. miR-223 appears to directly target PDGFRβ (in VSMCs) reversing the injury-induced dedifferentiation. Upon arterial injury platelet miR-223 knockout mice exhibit increased intimal hyperplasia, whereas miR-223 mimics reduced intimal hyperplasia. Diabetic mice with reduced expression of miR-223, exhibited enhanced VSMC dedifferentiation, proliferation, and increased intimal hyperplasia. Horizontal transfer of platelet-derived miRNAs into VSMCs provide a novel mechanism for regulating VSMC phenotypic switching. Platelets thus play a dual role in vascular injury repair, initiating an immediate repair process, and concurrently, a delayed process to prevent excessive repair.

Graphical Abstract
graphical abstract
Supplemental material

View Supplemental data not highlighted

Version history
  • Version 1 (January 15, 2019): In-Press Preview

Article tools

  • View PDF Adobe pdf file icon
  • Download citation information
  • Send a letter
  • License information
  • Standard abbreviations
  • Article usage
  • Citations to this article
  • Share this article
  • Need Help? E-mail the JCI

Go to:

  • Top
  • Abstract
  • Supplemental material
  • Version history
Advertisement
Advertisement
Follow JCI: Facebook logo white Twitter logo v2 Rss icon
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts