Signature of circulating microRNAs in patients with acute heart failure

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

doi:10.1002/ejhf.332

Signature of circulating microRNAs in patients with acute heart failure

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 GivertzPiotr Ponikowski, Peter van der Meer, Dirk J van Veldhuisen, Adriaan A Voors, Eugene Berezikov

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	414-23
Number of pages	10
Journal	European Journal of Heart Failure
Volume	18
Issue number	4
DOIs	https://doi.org/10.1002/ejhf.332
Publication status	Published - Apr 2016
Externally published	Yes

Keywords

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

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Ovchinnikova, E. S., Schmitter, D., Vegter, E. L., Ter Maaten, J. M., Valente, M. A. E., Liu, L. C. Y., van der Harst, P., Pinto, Y. M., de Boer, R. A., Meyer, S., Teerlink, J. R., O'Connor, C. M., Metra, M., Davison, B. A., Bloomfield, D. M., Cotter, G., Cleland, J. G., Mebazaa, A., Laribi, S., ... Berezikov, E. (2016). Signature of circulating microRNAs in patients with acute heart failure. European Journal of Heart Failure, 18(4), 414-23. https://doi.org/10.1002/ejhf.332

@article{3a7546ea06b74a01a7814c22dbec1e52,

title = "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.",

keywords = "Acute Disease, Aged, Aged, 80 and over, Case-Control Studies, Chronic Disease, Cohort Studies, Female, Heart Failure/blood, Humans, Male, MicroRNAs/blood, Middle Aged, Prognosis, Proportional Hazards Models, Pulmonary Disease, Chronic Obstructive/blood, Reverse Transcriptase Polymerase Chain Reaction",

author = "Ovchinnikova, {Ekaterina S} and Daniela Schmitter and Vegter, {Eline L} and {Ter Maaten}, {Jozine M} and Valente, {Mattia A E} and Liu, {Licette C Y} and {van der Harst}, Pim and Pinto, {Yigal M} and {de Boer}, {Rudolf A} and Sven Meyer and Teerlink, {John R} and O'Connor, {Christopher M} and Marco Metra and Davison, {Beth A} and Bloomfield, {Daniel M} and Gadi Cotter and Cleland, {John G} and Alexandre Mebazaa and Said Laribi and Givertz, {Michael M} and Piotr Ponikowski and {van der Meer}, Peter and {van Veldhuisen}, {Dirk J} and Voors, {Adriaan A} and Eugene Berezikov",

note = "{\textcopyright} 2015 The Authors European Journal of Heart Failure {\textcopyright} 2015 European Society of Cardiology.",

year = "2016",

month = apr,

doi = "10.1002/ejhf.332",

language = "English",

volume = "18",

pages = "414--23",

journal = "European Journal of Heart Failure",

issn = "1388-9842",

publisher = "Oxford University Press",

number = "4",

}

Ovchinnikova, ES, Schmitter, D, Vegter, EL, Ter Maaten, JM, Valente, MAE, Liu, LCY, van der Harst, P, Pinto, YM, de Boer, RA, Meyer, S, Teerlink, JR, O'Connor, CM, Metra, M, Davison, BA, Bloomfield, DM, Cotter, G, Cleland, JG, Mebazaa, A, Laribi, S, Givertz, MM, Ponikowski, P, van der Meer, P, van Veldhuisen, DJ, Voors, AA & Berezikov, E 2016, 'Signature of circulating microRNAs in patients with acute heart failure', European Journal of Heart Failure, vol. 18, no. 4, pp. 414-23. https://doi.org/10.1002/ejhf.332

TY - JOUR

T1 - Signature of circulating microRNAs in patients with acute heart failure

AU - Ovchinnikova, Ekaterina S

AU - Schmitter, Daniela

AU - Vegter, Eline L

AU - Ter Maaten, Jozine M

AU - Valente, Mattia A E

AU - Liu, Licette C Y

AU - van der Harst, Pim

AU - Pinto, Yigal M

AU - de Boer, Rudolf A

AU - Meyer, Sven

AU - Teerlink, John R

AU - O'Connor, Christopher M

AU - Metra, Marco

AU - Davison, Beth A

AU - Bloomfield, Daniel M

AU - Cotter, Gadi

AU - Cleland, John G

AU - Mebazaa, Alexandre

AU - Laribi, Said

AU - Givertz, Michael M

AU - Ponikowski, Piotr

AU - van der Meer, Peter

AU - van Veldhuisen, Dirk J

AU - Voors, Adriaan A

AU - Berezikov, Eugene

PY - 2016/4

Y1 - 2016/4

N2 - 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.

AB - 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.

KW - Acute Disease

KW - Aged

KW - Aged, 80 and over

KW - Case-Control Studies

KW - Chronic Disease

KW - Cohort Studies

KW - Female

KW - Heart Failure/blood

KW - Humans

KW - Male

KW - MicroRNAs/blood

KW - Middle Aged

KW - Prognosis

KW - Proportional Hazards Models

KW - Pulmonary Disease, Chronic Obstructive/blood

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1002/ejhf.332

DO - 10.1002/ejhf.332

M3 - Article

C2 - 26345695

SN - 1388-9842

VL - 18

SP - 414

EP - 423

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 4

ER -

Signature of circulating microRNAs in patients with acute heart failure

Abstract

Keywords

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