Ekaterina S Ovchinnikova1,2, Daniela Schmitter3, Eline L Vegter1, Jozine M Ter Maaten1, Mattia A E Valente1, Licette C Y Liu1, Pim van der Harst1, Yigal M Pinto4, Rudolf A de Boer1, Sven Meyer1, John R Teerlink5, Christopher M O'Connor6, Marco Metra7, Beth A Davison8, Daniel M Bloomfield9, Gadi Cotter8, John G Cleland10, Alexandre Mebazaa11, Said Laribi12, Michael M Givertz13, Piotr Ponikowski14, Peter van der Meer1, Dirk J van Veldhuisen1, Adriaan A Voors1, Eugene Berezikov2. 1. Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands. 2. European Research Institute for the Biology of Ageing and University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 3. Momentum Research, Inc., Allschwil, Switzerland. 4. University of Amsterdam, Amsterdam, The Netherlands. 5. University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA. 6. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. 7. Cardiology, The Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health; University of Brescia, Brescia, Italy. 8. Momentum Research, Durham, NC, USA. 9. Merck Research Laboratories, Rahway, NJ, USA. 10. National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College, London, UK. 11. University Paris Diderot, U942 INSERM, AP-HP, St Louis-Lariboisière University Hospitals, Department of Anesthesiology and Critical Care and Burn Unit, Paris, France. 12. U942 INSERM, AP-HP, St Louis-Lariboisière University Hospitals, Department of Emergency Medicine, Paris, France. 13. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 14. Medical University, Clinical Military Hospital, Wroclaw, Poland.
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.
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 CHFpatients or healthy subjects, whereas no significant changes were observed between acute COPDpatients 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: Thomas H Thatcher; Collynn F Woeller; Juilee Thakar; Atif Khan; Philip K Hopke; Matthew Ryan Smith; Karan Uppal; Douglas I Walker; Young-Mi Go; Dean P Jones; Pamela L Krahl; Timothy M Mallon; Patricia J Sime; Richard P Phipps; Mark J Utell Journal: J Occup Environ Med Date: 2019-12 Impact factor: 2.162
Authors: Collynn F Woeller; Thomas H Thatcher; Daniel Van Twisk; Stephen J Pollock; Amanda Croasdell; Nina Kim; Philip K Hopke; Xiaoyan Xia; Juilee Thakar; Col Timothy M Mallon; Mark J Utell; Richard P Phipps Journal: J Occup Environ Med Date: 2016-08 Impact factor: 2.162
Authors: Collynn F Woeller; Thomas H Thatcher; Daniel Van Twisk; Stephen J Pollock; Amanda Croasdell; Philip K Hopke; Xiaoyan Xia; Juilee Thakar; Patricia J Sime; Timothy M Mallon; Mark J Utell; Richard P Phipps Journal: J Occup Environ Med Date: 2016-08 Impact factor: 2.162