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

  • Lars Maegdefessel
  • Joshua M Spin
  • Uwe Raaz
  • Suzanne M Eken
  • Ryuji Toh
  • Junya Azuma
  • Matti Adam
  • Futoshi Nakagami
  • Futoshi Nagakami
  • Helen M Heymann
  • Ekaterina Chernogubova
  • Ekaterina Chernugobova
  • Hong Jin
  • Joy Roy
  • Rebecka Hultgren
  • Kenneth Caidahl
  • Sonja Schrepfer
  • Anders Hamsten
  • Per Eriksson
  • Michael V McConnell
  • Ronald L Dalman
  • Philip S Tsao

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.

Bibliographical data

Original languageEnglish
ISSN2041-1723
DOIs
Publication statusPublished - 31.10.2014
PubMed 25358394