Signature of circulating microRNAs in patients with acute heart failure.

Abstract

AIMS:

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

METHODS AND RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Ekaterina S Ovchinnikova, Daniela Schmitter, Eline L Vegter, Jozine M Ter Maaten, Mattia A E Valente, Licette C Y Liu, Pim van der Harst, Yigal M Pinto, Rudolf A de Boer, Sven Meyer, John R Teerlink, Christopher M O'Connor, Marco Metra, Beth A Davison, Daniel M Bloomfield, Gadi Cotter, John G Cleland, Alexandre Mebazaa, Said Laribi, Michael M Givertz, Piotr Ponikowski, Peter van der Meer, Dirk J van Veldhuisen, Adriaan A Voors, Eugene Berezikov
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 18 Issue 4 Pg. 414-23 (04 2016) ISSN: 1879-0844 [Electronic] England
• PMID: 26345695 (Publication Type: Journal Article)
• Copyright: © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Chemical References

• MIRN106 microRNA, human
• MIRN18A microRNA, human
• MIRN26A microRNA, human
• MIRN27 microRNA, human
• MIRN30b microRNA, human
• MIRN652 microRNA, human
• MicroRNAs
• mirn199 microRNA, human

Topics

• Acute Disease
• Aged
• Aged, 80 and over
• Case-Control Studies
• Chronic Disease
• Cohort Studies
• Female
• Heart Failure (blood, genetics, mortality)
• Humans
• Male
• MicroRNAs (blood)
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Pulmonary Disease, Chronic Obstructive (blood, genetics)
• Reverse Transcriptase Polymerase Chain Reaction