title: Cardiospecific microRNA plasma levels correlate with troponin and cardiac function in patients with ST elevation myocardial infarction, are selectively dependent on renal elimination, and can be detected in urine samples.
abstract: OBJECTIVE
  Circulating microRNAs (miRNAs) are promising as biomarkers for various diseases. We examined the release patterns of cardiospecific miRNAs in a closed-chest, large animal ischemia-reperfusion model and in patients with ST elevation myocardial infarction (STEMI).
  
  
  METHODS
  Six anesthetized pigs were subjected to coronary occlusion-reperfusion. Plasma, urine, and clinical parameters were collected from 25 STEMI patients undergoing primary percutaneous coronary intervention. miRNA was extracted and measured with qPCR.
  
  
  RESULTS
  In the pig reperfusion model miR-1, miR-133a, and miR-208b increased rapidly in plasma with a peak at 120 min, while miR-499-5p remained elevated longer. In patients with STEMI all 4 miRNAs increased abruptly from 70-fold to 3,000-fold in plasma, with a peak within 12 h (p < 0.01). miR-1 and miR-133a both correlated strongly with the glomerular filtration rate (GFR), indicating renal elimination. This was confirmed by detection of miR-1 and miR-133a, but not miR-208b or miR-499-5p, in urine. Peak values of miR-208b correlated with peak troponin and the ejection fraction.
  
  
  CONCLUSIONS
  We demonstrate a distinct and rapid increase in levels of cardiospecific miRNA in the circulation after myocardial infarction. Release of miRNAs correlated with cardiomyocyte necrosis markers, the ejection fraction, and the GFR, indicating a possible role for these molecules as biomarkers for the diagnosis of STEMI as well as the prediction of long-term complications.
authors.affiliation: Department of Cardiology, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Gidlöf
authors.forename: Patrik
authors.initials: P
authors.lastname: Andersson
authors.forename: Jesper
authors.initials: J
authors.lastname: van der Pals
authors.forename: Matthias
authors.initials: M
authors.lastname: Götberg
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000652:urine; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000473:pathology / Q000652:urine; D032383:Myocytes, Cardiac / Q000473:pathology; D009336:Necrosis; D012372:ROC Curve; D013318:Stroke Volume; D013552:Swine; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D020107:Troponin T