Signature of circulating microRNAs in patients with acute heart failure.
Our aim was to identify circulating microRNAs (miRNAs) associated with acute heart failure (AHF).



Plasma miRNA profiling included 137 patients with AHF from 3 different cohorts, 20 with chronic heart failure (CHF), 8 with acute exacerbation of COPD, and 41 healthy controls. Levels of circulating miRNAs were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Plasma levels of miRNAs in patients with AHF were decreased compared with CHF patients or healthy subjects, whereas no significant changes were observed between acute COPD patients and controls. Fifteen miRNAs found in the discovery phase to differ most significantly between healthy controls and patients with AHF were further investigated in an extended cohort of 100 AHF patients at admission and a separate cohort of 18 AHF patients at different time points. Out of these 15 miRNAs, 12 could be confirmed in an additional AHF validation cohort and 7 passed the Bonferroni correction threshold (miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-106a-5p, miR-199a-3p, and miR-652-3p, all P < 0.00005). A further drop in miRNA levels within 48 h after AHF admission was associated with an increased risk of 180-day mortality in a subset of the identified miRNAs.



Declining levels of circulating miRNAs were associated with increasing acuity of heart failure. Early in-hospital decreasing miRNA levels were predictive for mortality in a subset of miRNAs in patients with AHF. The discovered miRNA panel may serve as a launch-pad for molecular pathway studies to identify new pharmacological targets and miRNA-based therapies.
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.|European Research Institute for the Biology of Ageing and University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ekaterina S
ES
Ovchinnikova
Momentum Research, Inc., Allschwil, Switzerland.
Daniela
D
Schmitter
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Eline L
EL
Vegter
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Jozine M
JM
Ter Maaten
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Mattia A E
MA
Valente
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Licette C Y
LC
Liu
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Pim
P
van der Harst
University of Amsterdam, Amsterdam, The Netherlands.
Yigal M
YM
Pinto
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Rudolf A
RA
de Boer
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Sven
S
Meyer
University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
John R
JR
Teerlink
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
Christopher M
CM
O'Connor
Cardiology, The Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health; University of Brescia, Brescia, Italy.
Marco
M
Metra
Momentum Research, Durham, NC, USA.
Beth A
BA
Davison
Merck Research Laboratories, Rahway, NJ, USA.
Daniel M
DM
Bloomfield
Momentum Research, Durham, NC, USA.
Gadi
G
Cotter
National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College, London, UK.
John G
JG
Cleland
University Paris Diderot, U942 INSERM, AP-HP, St Louis-Lariboisière University Hospitals, Department of Anesthesiology and Critical Care and Burn Unit, Paris, France.
Alexandre
A
Mebazaa
U942 INSERM, AP-HP, St Louis-Lariboisière University Hospitals, Department of Emergency Medicine, Paris, France.
Said
S
Laribi
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Michael M
MM
Givertz
Medical University, Clinical Military Hospital, Wroclaw, Poland.
Piotr
P
Ponikowski
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Peter
P
van der Meer
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Dirk J
DJ
van Veldhuisen
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Adriaan A
AA
Voors
European Research Institute for the Biology of Ageing and University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Eugene
E
Berezikov
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs; C542541:MIRN106 microRNA, human; C522576:MIRN18A microRNA, human; C528163:MIRN26 microRNA, human; C531388:MIRN27 microRNA, human; C546086:MIRN30b microRNA, human; C574011:MIRN652 microRNA, human; C531408:mirn199 microRNA, human
Biomarkers; Circulating microRNAs; Heart failure