A unique MicroRNA signature associated with plaque instability in humans

Francesco Cipollone, Lara Felicioni, Riccardo Sarzani, Sante Ucchino, Francesco Spigonardo, Claudia Mandolini, Sara Malatesta, Marco Bucci, Chiara Mammarella, Donato Santovito, Federica De Lutiis, Antonio Marchetti, Andrea Mezzetti, Fiamma Buttitta

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Abstract

Background and Purpose-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.

Original languageEnglish
Pages (from-to)2556-2563
Number of pages8
JournalStroke
Volume42
Issue number9
DOIs
Publication statusPublished - Sep 2011

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Keywords

  • atherosclerosis
  • inflammation
  • microRNA
  • vulnerable plaque

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialised Nursing

Cite this

Cipollone, F., Felicioni, L., Sarzani, R., Ucchino, S., Spigonardo, F., Mandolini, C., Malatesta, S., Bucci, M., Mammarella, C., Santovito, D., De Lutiis, F., Marchetti, A., Mezzetti, A., & Buttitta, F. (2011). A unique MicroRNA signature associated with plaque instability in humans. Stroke, 42(9), 2556-2563. https://doi.org/10.1161/STROKEAHA.110.597575