title: Diagnostic potential of plasmatic MicroRNA signatures in stable and unstable angina.
abstract: OBJECTIVE
  We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina.
  
  
  METHODS
  An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated.
  
  
  RESULTS
  Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA.
  
  
  CONCLUSIONS
  This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.
authors.affiliation: Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Yuri
authors.initials: Y
authors.lastname: D'Alessandra
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Carena
authors.forename: Liana
authors.initials: L
authors.lastname: Spazzafumo
authors.forename: Federico
authors.initials: F
authors.lastname: Martinelli
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bassetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Devanna
authors.forename: Mara
authors.initials: M
authors.lastname: Rubino
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Marenzi
authors.forename: Gualtiero I
authors.initials: GI
authors.lastname: Colombo
authors.forename: Felice
authors.initials: F
authors.lastname: Achilli
authors.forename: Stefano
authors.initials: S
authors.lastname: Maggiolini
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Giulio
authors.initials: G
authors.lastname: Pompilio
mesh_terms: D000368:Aged; D060050:Angina, Stable / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D000789:Angina, Unstable / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D035683:MicroRNAs