Acute Loss of miR-221 and miR-222 in the Atherosclerotic Plaque Shoulder Accompanies Plaque Rupture

Stroke. 2015 Nov;46(11):3285-7. doi: 10.1161/STROKEAHA.115.010567. Epub 2015 Oct 8.


Background and purpose: Atherosclerotic plaque vulnerability is accompanied by changes in the molecular and cellular function in the plaque shoulder, including a decrease in vascular smooth muscle cell proliferation. We aimed to determine whether the expression of 3 miRNAs that regulate vascular smooth muscle cell proliferation (miR-145, miR-221, and miR-222) is altered with plaque rupture, suggesting a role in regulating plaque stability.

Methods: miRNAs were measured in the plaque shoulder of carotid plaques obtained from patients undergoing carotid endarterectomy (CEA) for 3 distinct clinical scenarios: (1) patients without previous neurological events but high-grade carotid stenosis (asymptomatic), (2) patients with an acute neurological event within 5 days of the CEA (urgent), and (3) patients undergoing CEA>5 days after a neurological event (symptomatic).

Results: Mean time from plaque rupture event to CEA was 2.4 days in the urgent group. The urgent group exhibited a significant decrease in miR-221 and miR-222 expression in the plaque shoulder, whereas no significant differences were seen in miR-145 across the 3 groups. Regression analysis demonstrated a significant correlation between time from the neurological event to CEA and increasing miR-221 and miR-222, but not miR-145. mRNA encoding p27Kip1, a target of miR-221 and miR-222 that inhibits vascular smooth muscle cell proliferation, was increased in the urgent group.

Conclusions: Atherosclerotic plaque rupture is accompanied by a loss of miR-221 and miR-222 and an increase in p27Kip1 mRNA expression in the plaque shoulder, suggesting an association between these miRNAs and atherosclerotic plaque stability.

Keywords: atherosclerosis; carotid stenosis; endarterectomy, carotid; microRNAs; muscle, smooth, vascular.

Publication types

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

MeSH terms

  • Aged
  • Asymptomatic Diseases*
  • Carotid Stenosis / genetics*
  • Carotid Stenosis / surgery
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Endarterectomy, Carotid
  • Female
  • Gene Expression Profiling
  • Humans
  • Linear Models
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • Muscle, Smooth, Vascular / metabolism
  • Plaque, Atherosclerotic / genetics*
  • Plaque, Atherosclerotic / surgery
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Rupture, Spontaneous
  • STAT5 Transcription Factor / genetics
  • Stem Cell Factor / genetics
  • Tumor Suppressor Proteins / genetics


  • MIRN145 microRNA, human
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Stem Cell Factor
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27