MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions

Circ Res. 2017 Feb 17;120(4):633-644. doi: 10.1161/CIRCRESAHA.116.309318. Epub 2016 Nov 28.


Rationale: In the search for markers and modulators of vascular disease, microRNAs (miRNAs) have emerged as potent therapeutic targets.

Objective: To investigate miRNAs of clinical interest in patients with unstable carotid stenosis at risk of stroke.

Methods and results: Using patient material from the BiKE (Biobank of Karolinska Endarterectomies), we profiled miRNA expression in patients with stable versus unstable carotid plaque. A polymerase chain reaction-based miRNA array of plasma, sampled at the carotid lesion site, identified 8 deregulated miRNAs (miR-15b, miR-29c, miR-30c/d, miR-150, miR-191, miR-210, and miR-500). miR-210 was the most significantly downregulated miRNA in local plasma material. Laser capture microdissection and in situ hybridization revealed a distinct localization of miR-210 in fibrous caps. We confirmed that miR-210 directly targets the tumor suppressor gene APC (adenomatous polyposis coli), thereby affecting Wnt (Wingless-related integration site) signaling and regulating smooth muscle cell survival, as well as differentiation in advanced atherosclerotic lesions. Substantial changes in arterial miR-210 were detectable in 2 rodent models of vascular remodeling and plaque rupture. Modulating miR-210 in vitro and in vivo improved fibrous cap stability with implications for vascular disease.

Conclusions: An unstable carotid plaque at risk of stroke is characterized by low expression of miR-210. miR-210 contributes to stabilizing carotid plaques through inhibition of APC, ensuring smooth muscle cell survival. We present local delivery of miR-210 as a therapeutic approach for prevention of atherothrombotic vascular events.

Keywords: adenomatous polyposis coli; atherosclerosis; carotid stenosis; microRNAs; stroke.

MeSH terms

  • Animals
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / therapy
  • Carotid Stenosis / metabolism
  • Carotid Stenosis / pathology
  • Carotid Stenosis / therapy
  • Cells, Cultured
  • Cohort Studies
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Humans
  • Laser Capture Microdissection / methods
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / administration & dosage*
  • MicroRNAs / analysis
  • MicroRNAs / biosynthesis*
  • Plaque, Atherosclerotic / metabolism*
  • Plaque, Atherosclerotic / pathology
  • Plaque, Atherosclerotic / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Stroke / metabolism
  • Stroke / pathology
  • Stroke / prevention & control


  • MIRN210 microRNA, human
  • MicroRNAs