miR-619-5p and cardiogenic shock in patients with ST-segment elevation myocardial infarction.

cardiovascular disease epigenetic inflammatory response mortality risk plasma miRNAs

Journal

European journal of clinical investigation
ISSN: 1365-2362
Titre abrégé: Eur J Clin Invest
Pays: England
ID NLM: 0245331

Informations de publication

Date de publication:
20 Feb 2024
Historique:
revised: 12 02 2024
received: 14 12 2023
accepted: 13 02 2024
medline: 20 2 2024
pubmed: 20 2 2024
entrez: 20 2 2024
Statut: aheadofprint

Résumé

Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST-segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI-patients. STEMI-patients (n = 49), with (CS, n = 25) and without CS (non-CS, n = 24) fulfilling inclusion criteria were included from HSCSP-cohort (Derivation-cohort). CS-miRNAs were analysed by Affymetrix-microarray and RT-PCR. Results were validated in a second cohort of CS-patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes. Of the 5-miRNA signature obtained from microarray analysis, miR-619-5p showed higher levels in CS than in Non-CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR-619-5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR-619-5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP-cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock-cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR-619-5p target genes and TNF-alpha were involved in the regulation of inflammation. miR-619-5p and TNF-alpha levels discriminated mortality outcome in CS-patients during 30-day follow-up (Validation-Cohort: ROC: .812, p = .002; HR: 9.99, p = .003). Up-regulation of miR-619-5p is found in the plasma of STEMI-patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI.

Sections du résumé

BACKGROUND BACKGROUND
Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST-segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI-patients.
METHODS METHODS
STEMI-patients (n = 49), with (CS, n = 25) and without CS (non-CS, n = 24) fulfilling inclusion criteria were included from HSCSP-cohort (Derivation-cohort). CS-miRNAs were analysed by Affymetrix-microarray and RT-PCR. Results were validated in a second cohort of CS-patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes.
RESULTS RESULTS
Of the 5-miRNA signature obtained from microarray analysis, miR-619-5p showed higher levels in CS than in Non-CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR-619-5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR-619-5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP-cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock-cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR-619-5p target genes and TNF-alpha were involved in the regulation of inflammation. miR-619-5p and TNF-alpha levels discriminated mortality outcome in CS-patients during 30-day follow-up (Validation-Cohort: ROC: .812, p = .002; HR: 9.99, p = .003).
CONCLUSIONS CONCLUSIONS
Up-regulation of miR-619-5p is found in the plasma of STEMI-patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI.

Identifiants

pubmed: 38376079
doi: 10.1111/eci.14186
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e14186

Subventions

Organisme : Agencia Estatal de Investigación
ID : 10.13039/501100011033-[PID2019-107160RB-I00]
Organisme : Instituto de Salud Carlos III
ID : PI22/01930
Organisme : Instituto de Salud Carlos III
ID : Red RICORS TERAV- RD21/0017/0013
Organisme : Spanish Society of Cardiology (SEC)
ID : Investigación Clínica (2015)

Informations de copyright

© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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Auteurs

Rafael Escate (R)

Cardiovascular-Program ICCC, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain.
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.

Teresa Padró (T)

Cardiovascular-Program ICCC, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain.
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.

Rosa Suades (R)

Cardiovascular-Program ICCC, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain.

Jordi Sans-Roselló (J)

Cardiology Department, Parc Taulí Hospital Universitari, Sabadell, Spain.

Yvan Devaux (Y)

Cardiovascular Research Unit, Luxembourg Institute of Health, Strassen, Luxembourg.

Päivi Lakkisto (P)

Department of Clinical Chemistry and Hematology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Minerva Foundation Institute for Medical Research, Helsinki, Finland.

Veli-Pekka Harjola (VP)

Emergency Medicine, Department of Emergency Services and Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Alessandro Sionis (A)

Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
Acute and Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain.
Universidad Autónoma de Barcelona, Barcelona, Spain.

Lina Badimon (L)

Cardiovascular-Program ICCC, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain.
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
Cardiovascular Research Chair, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

Classifications MeSH