title: MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease.
abstract: BACKGROUND
  Circulating microRNAs (miRNAs) are differentially regulated and selectively packaged in microvesicles (MVs). We evaluated whether circulating vascular and endothelial miRNAs in patients with stable coronary artery disease have prognostic value for the occurrence of cardiovascular (CV) events.
  
  
  RESULTS
  Ten miRNAs involved in the regulation of vascular performance-miR-126, miR-222, miR-let7d, miR-21, miR-20a, miR-27a, miR-92a, miR-17, miR-130, and miR-199a-were quantified in plasma and circulating MVs by reverse transcription polymerase chain reaction in 181 patients with stable coronary artery disease. The median duration of follow-up for major adverse CV event-free survival was 6.1 years (range: 6.0-6.4 years). Events occurred in 55 patients (31.3%). There was no significant association between CV events and plasma level of the selected miRNAs. In contrast, increased expression of miR-126 and miR-199a in circulating MVs was significantly associated with a lower major adverse CV event rate. In univariate analysis, above-median levels of miR-126 in circulating MVs were predictors of major adverse CV event-free survival (hazard ratio: 0.485 [95% CIAUTHOR: Is 95% CI correct?: 0.278 to 0.846]; P=0.007) and percutaneous coronary interventions (hazard ratio: 0.458 [95% CI: 0.222 to 0.945]; P=0.03). Likewise, an increased level of miR-199a in circulating MVs was associated with a reduced risk of major adverse CV events (hazard ratio: 0.518 [95% CI: 0.299 to 0.898]; P=0.01) and revascularization (hazard ratio: 0.439 [95% CI: 0.232 to 0.832]; P=0.01) in univariate analysis. miRNA expression analysis in plasma compartments revealed that miR-126 and miR-199a are present mainly in circulating MVs. MV-sorting experiments showed that endothelial cells and platelets were found to be the major cell sources of MVs containing miR-126 and miR-199a, respectively.
  
  
  CONCLUSIONS
  MVs containing miR-126 and miR-199a but not freely circulating miRNA expression predict the occurrence of CV events in patients with stable coronary artery disease.
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: Felix
authors.initials: F
authors.lastname: Jansen
authors.affiliation: Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL (X.Y.).
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: Sebastian
authors.initials: S
authors.lastname: Proebsting
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: Marion
authors.initials: M
authors.lastname: Hoelscher
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: David
authors.initials: D
authors.lastname: Przybilla
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: Katharina
authors.initials: K
authors.lastname: Baumann
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: Theresa
authors.initials: T
authors.lastname: Schmitz
authors.affiliation: Institute of Molecular Medicine, Rheinische Friedrich-Wilhelms University, Bonn, Germany (A.D., E.E.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Dolf
authors.affiliation: Institute of Molecular Medicine, Rheinische Friedrich-Wilhelms University, Bonn, Germany (A.D., E.E.).
authors.forename: Elmar
authors.initials: E
authors.lastname: Endl
authors.affiliation: Institute of Innate Immunity, Rheinische Friedrich-Wilhelms University, Bonn, Germany (B.S.F.).
authors.forename: Bernardo S
authors.initials: BS
authors.lastname: Franklin
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: Jan-Malte
authors.initials: JM
authors.lastname: Sinning
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: Mariuca
authors.initials: M
authors.lastname: Vasa-Nicotera
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.affiliation: Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany (F.J., S.P., M.H., D.P., K.B., T.S., J.M.S., M.V.N., G.N., N.W.).
authors.forename: Nikos
authors.initials: N
authors.lastname: Werner
mesh_terms: D000368:Aged; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D005819:Genetic Markers; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; C531408:mirn199 microRNA, human
keywords: coronary artery disease; microRNA; microvesicles; prognosis