title: A unique microRNA signature associated with plaque instability in humans.
abstract: OBJECTIVE
  Atherosclerotic plaque rupture is considered the most important mechanism that underlies the onset of stroke, myocardial infarction, and sudden death. Several evidences demonstrated the pivotal role of inflammatory processes in plaque destabilization. MicroRNAs (miRNAs) are small endogenous RNAs and represent a new important class of gene regulators. Nevertheless, no data exist about the expression profile of miRNAs in atherosclerotic plaques. Thus, the aim of this study was to investigate the expression level of miRNAs in human plaques and to correlate it with clinical features of plaque destabilization.
  
  
  METHODS
  Two separate groups of plaques were collected from patients who underwent carotid endarterectomy in Chieti (n=15) and Ancona (n=38) Hospitals. All the plaques were subdivided in symptomatic (n=22) and asymptomatic (n=31) according to the presence/absence of stroke.
  
  
  RESULTS
  First, on the plaques collected at Chieti Hospital, we performed large-scale analysis of miRNA expression. Between the 41 miRNAs examined, we discovered profound differences in the expression of 5 miRNAs (miRNA-100, miRNA-127, miRNA-145, miRNA-133a, and miRNA-133b) in symptomatic versus asymptomatic plaques. Remarkably, when we repeated the analysis on the Ancona plaque subset, all these 5 miRNAs confirmed to be significantly more expressed in the symptomatic plaques. Finally, in vitro experiments on endothelial cells transfected with miRNA-145 and miRNA-133a confirmed the importance of these miRNAs in the modulation of stroke-related proteins.
  
  
  CONCLUSIONS
  These results are the first to report alterations in the expression of specific miRNAs in human atherosclerotic plaques and suggest that miRNAs may have an important role in regulating the evolution of atherosclerotic plaque toward instability and rupture. Furthermore, by identifying the specific miRNA signature for stroke now, we are able to use computer algorithms to identify previously unrecognized molecular targets.
authors.affiliation: Centro di Eccellenza Europeo e di Riferimento Regionale per l'Aterosclerosi, l'Ipertensione Arteriosa e le Dislipidemie, Nuovo Policlinico SS, Annunziata, Via dei Vestini 66, 66013 Chieti, Italy. fcipollone@unich.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Cipollone
authors.forename: Lara
authors.initials: L
authors.lastname: Felicioni
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sarzani
authors.forename: Sante
authors.initials: S
authors.lastname: Ucchino
authors.forename: Francesco
authors.initials: F
authors.lastname: Spigonardo
authors.forename: Claudia
authors.initials: C
authors.lastname: Mandolini
authors.forename: Sara
authors.initials: S
authors.lastname: Malatesta
authors.forename: Marco
authors.initials: M
authors.lastname: Bucci
authors.forename: Chiara
authors.initials: C
authors.lastname: Mammarella
authors.forename: Donato
authors.initials: D
authors.lastname: Santovito
authors.forename: Federica
authors.initials: F
authors.lastname: de Lutiis
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Mezzetti
authors.forename: Fiamma
authors.initials: F
authors.lastname: Buttitta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D002478:Cells, Cultured; D015331:Cohort Studies; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery
chemical_list: D035683:MicroRNAs