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miR-619-5p and cardiogenic shock in patients with ST-segment elevation myocardial infarction
Rafael Escate1,2, Teresa Padró1,2, Rosa Suades1
1Cardiovascular-Program ICCC, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain.
Insights
Elevated miR-619-5p levels in ST-segment elevation myocardial infarction (STEMI) patients indicate cardiogenic shock (CS) and predict mortality. This highlights epigenetic regulation of inflammation in myocardial infarction severity.
Area of Science:
- Biochemistry
- Genetics
- Cardiology
Background:
- Cardiogenic shock (CS) is a severe complication of ST-segment elevation myocardial infarction (STEMI) with high mortality.
- Epigenetic factors in CS remain largely unexplored.
- This study investigates plasma microRNAs (miRNAs) in STEMI patients with and without CS.
Purpose of the Study:
- To identify plasma miRNA signatures associated with cardiogenic shock in STEMI patients.
- To evaluate the potential of these miRNAs as biomarkers for CS stratification and mortality prediction.
- To explore the role of epigenetic regulation in the severity of myocardial infarction.
Main Methods:
- Analysis of plasma miRNAs using microarray and RT-PCR in STEMI patients (n=49) stratified by CS presence.
- Validation of findings in an independent cohort of CS patients (n=35).
- In silico analysis to identify target genes of identified miRNAs.
Main Results:
- A 5-miRNA signature was identified, with miR-619-5p significantly elevated in CS patients (p=.003) and discriminating CS (AUC=.752).
- miR-619-5p levels correlated with risk scores (GRACE, CardShock) and predicted mortality in CS patients (AUCs > .73).
- In silico analysis suggested miR-619-5p and TNF-alpha are involved in inflammation, discriminating mortality in CS patients (HR=9.99).
Conclusions:
- Up-regulation of miR-619-5p in plasma is associated with cardiogenic shock and mortality in STEMI patients.
- miR-619-5p serves as a potential biomarker for CS and prognosis in STEMI.
- Epigenetic regulation of inflammation plays a specific role in myocardial infarction severity.
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.
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