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miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development

Author

Listed:
  • Lars Maegdefessel

    (Stanford University, Falk CVRB, 300 Pasteur Drive
    Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital)

  • Joshua M. Spin

    (Stanford University, Falk CVRB, 300 Pasteur Drive
    VA Palo Alto Health Care System, 3801 Miranda Avenue)

  • Uwe Raaz

    (Stanford University, Falk CVRB, 300 Pasteur Drive)

  • Suzanne M. Eken

    (Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital)

  • Ryuji Toh

    (Stanford University, Falk CVRB, 300 Pasteur Drive)

  • Junya Azuma

    (Center of Medical Innovation and Translational Research, Osaka University, 2-2 Yamada-oka)

  • Matti Adam

    (Stanford University, Falk CVRB, 300 Pasteur Drive)

  • Futoshi Nagakami

    (Stanford University, Falk CVRB, 300 Pasteur Drive)

  • Helen M. Heymann

    (Stanford University, Falk CVRB, 300 Pasteur Drive)

  • Ekaterina Chernugobova

    (Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital)

  • Hong Jin

    (Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital)

  • Joy Roy

    (Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital)

  • Rebecka Hultgren

    (Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital)

  • Kenneth Caidahl

    (Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital)

  • Sonja Schrepfer

    (Transplant and Stem Cell Immunology Laboratory, University Heart Center Hamburg, Martinistraße 52)

  • Anders Hamsten

    (Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital)

  • Per Eriksson

    (Center for Molecular Medicine L8:03, Karolinska Institute and University Hospital)

  • Michael V. McConnell

    (Stanford University, Falk CVRB, 300 Pasteur Drive)

  • Ronald L. Dalman

    (Stanford University, 300 Pasteur Drive)

  • Philip S. Tsao

    (Stanford University, Falk CVRB, 300 Pasteur Drive
    VA Palo Alto Health Care System, 3801 Miranda Avenue)

Abstract

Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRNAs) are crucial regulators of cardiovascular pathology and represent intriguing targets to limit AAA expansion. Here we show, by using two established murine models of AAA disease along with human aortic tissue and plasma analysis, that miR-24 is a key regulator of vascular inflammation and AAA pathology. In vivo and in vitro studies reveal chitinase 3-like 1 (Chi3l1) to be a major target and effector under the control of miR-24, regulating cytokine synthesis in macrophages as well as their survival, promoting aortic smooth muscle cell migration and cytokine production, and stimulating adhesion molecule expression in vascular endothelial cells. We further show that modulation of miR-24 alters AAA progression in animal models, and that miR-24 and CHI3L1 represent novel plasma biomarkers of AAA disease progression in humans.

Suggested Citation

  • Lars Maegdefessel & Joshua M. Spin & Uwe Raaz & Suzanne M. Eken & Ryuji Toh & Junya Azuma & Matti Adam & Futoshi Nagakami & Helen M. Heymann & Ekaterina Chernugobova & Hong Jin & Joy Roy & Rebecka Hul, 2014. "miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6214
    DOI: 10.1038/ncomms6214
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