title: Acute Loss of miR-221 and miR-222 in the Atherosclerotic Plaque Shoulder Accompanies Plaque Rupture.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Section of Vascular and Endovascular Surgery, Department of Surgery (H.A.B., A.J.B.) and Laboratory of Molecular Cardiology (C.B.O.), Ochsner Clinic, New Orleans, LA; and Tulane Heart and Vascular Institute and the Department of Physiology, Tulane School of Medicine, New Orleans, LA (S.A.H., A.J.B., D.L., T.C.W.).
authors.forename: Hernan A
authors.initials: HA
authors.lastname: Bazan
authors.affiliation: From the Section of Vascular and Endovascular Surgery, Department of Surgery (H.A.B., A.J.B.) and Laboratory of Molecular Cardiology (C.B.O.), Ochsner Clinic, New Orleans, LA; and Tulane Heart and Vascular Institute and the Department of Physiology, Tulane School of Medicine, New Orleans, LA (S.A.H., A.J.B., D.L., T.C.W.).
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Hatfield
authors.affiliation: From the Section of Vascular and Endovascular Surgery, Department of Surgery (H.A.B., A.J.B.) and Laboratory of Molecular Cardiology (C.B.O.), Ochsner Clinic, New Orleans, LA; and Tulane Heart and Vascular Institute and the Department of Physiology, Tulane School of Medicine, New Orleans, LA (S.A.H., A.J.B., D.L., T.C.W.).
authors.forename: Chasity B
authors.initials: CB
authors.lastname: O'Malley
authors.affiliation: From the Section of Vascular and Endovascular Surgery, Department of Surgery (H.A.B., A.J.B.) and Laboratory of Molecular Cardiology (C.B.O.), Ochsner Clinic, New Orleans, LA; and Tulane Heart and Vascular Institute and the Department of Physiology, Tulane School of Medicine, New Orleans, LA (S.A.H., A.J.B., D.L., T.C.W.).
authors.forename: Ashton J
authors.initials: AJ
authors.lastname: Brooks
authors.affiliation: From the Section of Vascular and Endovascular Surgery, Department of Surgery (H.A.B., A.J.B.) and Laboratory of Molecular Cardiology (C.B.O.), Ochsner Clinic, New Orleans, LA; and Tulane Heart and Vascular Institute and the Department of Physiology, Tulane School of Medicine, New Orleans, LA (S.A.H., A.J.B., D.L., T.C.W.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Lightell
authors.affiliation: From the Section of Vascular and Endovascular Surgery, Department of Surgery (H.A.B., A.J.B.) and Laboratory of Molecular Cardiology (C.B.O.), Ochsner Clinic, New Orleans, LA; and Tulane Heart and Vascular Institute and the Department of Physiology, Tulane School of Medicine, New Orleans, LA (S.A.H., A.J.B., D.L., T.C.W.). Twoods3@tulane.edu.
authors.forename: T Cooper
authors.initials: TC
authors.lastname: Woods
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D016893:Carotid Stenosis / Q000235:genetics* / Q000601:surgery; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D016894:Endarterectomy, Carotid; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016014:Linear Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012422:Rupture, Spontaneous; D050799:STAT5 Transcription Factor / Q000235:genetics; D019089:Stem Cell Factor / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D035683:MicroRNAs; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D019089:Stem Cell Factor; D025521:Tumor Suppressor Proteins; C541010:MIRN145 microRNA, human; C525709:MIR221, human; C525710:MIR222, human; C494092:STAT5A protein, human
keywords: atherosclerosis; carotid stenosis; endarterectomy, carotid; microRNAs; muscle, smooth, vascular