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

Nat Commun. 2014 Oct 31;5:5214. doi: 10.1038/ncomms6214.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / metabolism
  • Aortic Aneurysm, Abdominal / etiology
  • Aortic Aneurysm, Abdominal / metabolism*
  • Biomarkers / blood
  • Cells, Cultured
  • Chitinase-3-Like Protein 1
  • Disease Models, Animal
  • Disease Progression
  • Endothelial Cells / metabolism*
  • Glycoproteins / metabolism
  • Humans
  • Inflammation / metabolism
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Myocytes, Smooth Muscle / metabolism*

Substances

  • Biomarkers
  • Chil1 protein, mouse
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • MicroRNAs
  • Mirn24 microRNA, mouse

Associated data

  • GEO/GSE51229