title: Transcoronary concentration gradients of circulating microRNAs.
abstract: BACKGROUND
  Circulating levels of microRNA (miR) have been proposed as biomarkers for cardiovascular disease. To identify the heart as a potential source for miRs released into the circulation, we measured concentration gradients across the coronary circulation for muscle-enriched (miR-133a, miR-499, miR-208a), vascular (miR-126, miR-92a), leukocyte-related (miR-155), and platelet-enriched (miR-223) miRs.
  
  
  RESULTS
  Circulating miRs were measured by TaqMan polymerase chain reaction in EDTA-plasma simultaneously obtained from the aorta and the coronary venous sinus in patients without coronary artery disease (n=7), with stable coronary artery disease (n=31), and with troponin-positive acute coronary syndromes (n=19). Circulating levels of the muscle-enriched miR-499 (>20-fold; P<0.01), miR-133a (11-fold; P<0.01), and miR-208a (5-fold; P<0.01) were significantly elevated in the aorta of troponin-positive acute coronary syndrome patients compared with patients with coronary artery disease. Importantly, there was a significant increase in circulating levels of miR-499 and miR-133a across the coronary circulation in troponin-positive acute coronary syndrome patients, suggestive of a release into the coronary circulation during myocardial injury. Indeed, miR-499 concentration gradients were significantly correlated with the extent of myocardial damage as measured by high-sensitivity troponin T (r=0.70, P<0.01). In contrast, circulating levels of miR-126 (P=0.16) decreased during transcoronary passage in patients with evidence of myocardial injury, suggesting consumption during transcoronary passage.
  
  
  CONCLUSIONS
  Muscle-enriched miR-499 and miR-133a are released from the heart into the coronary circulation on myocardial injury, whereas the vascular miR-126 is consumed during transcoronary passage. The differential regulation of circulating miRs during the transcoronary passage might provide important insights to exploit their role as cardiac biomarkers. Clinical Trial Registration- URL: http://www.germanctr.de. Unique identifier: DRKS00000207; in German Clinical Trials Registry.
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Rosa
authors.forename: Stephan
authors.initials: S
authors.lastname: Fichtlscherer
authors.forename: Ralf
authors.initials: R
authors.lastname: Lehmann
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmus
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D006328:Cardiac Catheterization; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D003326:Coronary Circulation / Q000502:physiology*; D054326:Coronary Sinus / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D020107:Troponin T; C527111:MIRN126 microRNA, human; C548234:MIRN133 microRNA, human; C524942:MIRN155 microRNA, human; C550906:MIRN208 microRNA, human; C525067:MIR223, human; C548683:MIRN499 microRNA, human; C541874:MIRN92 microRNA, human