title: Transcoronary gradients of vascular miRNAs and coronary atherosclerotic plaque characteristics.
abstract: Circulating microRNAs (miRs) may reflect pathophysiologically relevant processes in the atherosclerotically diseased coronary arterial wall. Given the unmet medical need to identify patients with an unstable plaque phenotype, we determined the relation of circulating atherosclerosis-regulatory miRs with plaque phenotypes.
  
  
  
  We assessed coronary atherosclerotic plaque burden and phenotype by optical coherence tomography in 52 patients and measured the levels of circulating miRs across the transcoronary gradient. The overall plaque load was significantly correlated with transcoronary concentration gradients of miR-126-3p (P = 0.04), miR-145-5p (P = 0.01), miR-155-5p (P < 0.01), and miR-29b-3p (P = 0.02), but not with other miRs such as miR-92a-3p. In patients with a high extent of vulnerable plaques as assessed by the presence of thin-cap fibroatheromas (TCFAs), significantly higher transcoronary gradients were observed, particularly for miR-126-3p, miR-126-5p, and miR-145-5p (all P < 0.02). Transcoronary gradients of miR-126-3p (P < 0.01), miR-126-5p (P < 0.01), miR-145-5p (P = 0.01), miR-29b-3p (P = 0.03), and miR-155-5p (P = 0.02) demonstrated a significant discriminatory power to predict the presence of TCFAs (AUC > 0.7 for all). Moreover, aortic and venous coronary sinus levels of miR-29b-3p were inversely correlated with plaque fibrosis, a finding that is consistent with the anti-fibrotic activity of miR-29b-3p.
  
  
  
  The overall plaque burden and plaque phenotypes are associated with changes in the kinetics of miR-concentrations across the transcoronary passage. Transcoronary gradients of the anti-atherosclerotic miR-126-3p and miR-145-5p correlated with the extent of TCFAs, suggesting that instable plaques may affect the local uptake or degradation of these miRs.
authors.affiliation: Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Leistner
authors.affiliation: Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany German Center of Cardiovascular Research (DZHK), Site RheinMain, 60590 Frankfurt am Main, Germany.
authors.forename: Jes-Niels
authors.initials: JN
authors.lastname: Boeckel
authors.affiliation: Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.
authors.forename: Sophia M
authors.initials: SM
authors.lastname: Reis
authors.affiliation: Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Thome
authors.affiliation: Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Roberta
authors.initials: R
authors.lastname: De Rosa
authors.affiliation: Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany German Center of Cardiovascular Research (DZHK), Site RheinMain, 60590 Frankfurt am Main, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Keller
authors.affiliation: Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany German Center of Cardiovascular Research (DZHK), Site RheinMain, 60590 Frankfurt am Main, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Palapies
authors.affiliation: Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Fichtlscherer
authors.affiliation: Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany German Center of Cardiovascular Research (DZHK), Site RheinMain, 60590 Frankfurt am Main, Germany dimmeler@em.uni-frankfurt.de.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.affiliation: Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany German Center of Cardiovascular Research (DZHK), Site RheinMain, 60590 Frankfurt am Main, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D050197:Atherosclerosis; D003331:Coronary Vessels; D006321:Heart; D006801:Humans; D035683:MicroRNAs; D058226:Plaque, Atherosclerotic
chemical_list: D035683:MicroRNAs
keywords: Biomarker; C7-XR™ OCT system; Circulating miRNA; Coronary angiography; Coronary atherosclerotic plaque characteristics; MicroRNA; OCT; Optical coherence tomography; TCFA; Thin-cap fibroatheromas; Transcoronary miRNA gradient; Vulnerable plaque biomarker; Vulnerable plaques; miR; miR-126; miR-126-3p; miR-145; miR-145-5p; miR-155-5p; miR-29b; miR-29b-3p; miR-92a; miRNA