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

Rafael Escate; Teresa Padró; Rosa Suades; Jordi Sans-Roselló; Yvan Devaux; Päivi Lakkisto; Veli-Pekka Harjola; Alessandro Sionis; Lina Badimon

doi:10.1111/eci.14186

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

Eur J Clin Invest. 2024 Feb 20:e14186. doi: 10.1111/eci.14186. Online ahead of print.

Authors

Rafael Escate^{1

2}, Teresa Padró^{1

2}, Rosa Suades¹, Jordi Sans-Roselló³, Yvan Devaux⁴, Päivi Lakkisto^{5

6}, Veli-Pekka Harjola⁷, Alessandro Sionis^{2

8

9}, Lina Badimon^{1

2

10}

Affiliations

¹ Cardiovascular-Program ICCC, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain.
² Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
³ Cardiology Department, Parc Taulí Hospital Universitari, Sabadell, Spain.
⁴ Cardiovascular Research Unit, Luxembourg Institute of Health, Strassen, Luxembourg.
⁵ Department of Clinical Chemistry and Hematology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁶ Minerva Foundation Institute for Medical Research, Helsinki, Finland.
⁷ Emergency Medicine, Department of Emergency Services and Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁸ Acute and Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain.
⁹ Universidad Autónoma de Barcelona, Barcelona, Spain.
¹⁰ Cardiovascular Research Chair, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

PMID: 38376079
DOI: 10.1111/eci.14186

Abstract

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: 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: 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: 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.

Keywords: cardiovascular disease; epigenetic; inflammatory response; mortality risk; plasma miRNAs.

Abstract

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