Abstract
Restoration of epicardial coronary blood flow, achieved by early reperfusion with primary percutaneous coronary intervention (PPCI), is the guideline recommended to treat patients with ST-segment-elevation myocardial infarction (STEMI). However, despite successful blood restoration, increasing numbers of patients develop left ventricular adverse remodelling (LVAR) and heart failure. Therefore, reliable prognostic biomarkers for LVAR in STEMI are urgently needed. Our aim was to investigate the role of circulating microRNAs (miRNAs) and their association with LVAR in STEMI patients following the PPCI procedure. We analysed the expression of circulating miRNAs in blood samples of 56 patients collected at admission and after revascularization (at 3, 6, 12 and 24 h). The associations between miRNAs and left ventricular end diastolic volumes at 6 months were estimated to detect LVAR. miRNAs were also analysed in samples isolated from peripheral blood mononuclear cells (PBMCs) and human myocardium of failing hearts. Kinetic analysis of miRNAs showed a fast time-dependent increase in miR-133a, miR-133b, miR-193b, miR-499, and miR-320a in STEMI patients compared to controls. Moreover, the expression of miR-29a, miR-29b, miR-324, miR-208, miR-423, miR-522, and miR-545 was differentially expressed even before PPCI in STEMI. Furthermore, the increase in circulating miR-320a and the decrease in its expression in PBMCs were significantly associated with LVAR and correlated with the expression of miR-320a in human failing myocardium from ischaemic origin. In conclusion, we determined the time course expression of new circulating miRNAs in patients with STEMI treated with PPCI and we showed that miR-320a was positively associated with LVAR.
Highlights
ST-segment-elevation myocardial infarction (STEMI) is considered the most common and severe acute myocardial infarction (AMI) [1]
Samples from control and STEMI patients with thrombolysis in myocardial infarction (TIMI) 0 flow were used to detect the profiles of miRNAs secreted in the serum 3 to 6 h after primary percutaneous coronary intervention (PPCI) by a RT-qPCR-based array
The hierarchical clustering analysis indicated that 25 miRNAs were differentially expressed despite the variability between STEMI patient samples compared to the control group (Figure 1B)
Summary
ST-segment-elevation myocardial infarction (STEMI) is considered the most common and severe acute myocardial infarction (AMI) [1]. Early reperfusion of coronary flow by primary percutaneous coronary intervention (PPCI) significantly mitigates cardiac cell death and cardiovascular events. STEMI treated with PPCI triggers a complex cascade of events associated with ischaemia and reperfusion (I/R), such as oxidative stress, neutrophil and platelet aggregation, and acute inflammatory responses [8] necessary to repair heart injuries. Peripheral blood mononuclear cells (PBMCs), mainly monocytes, participate in the acute response to heart damage. These cell populations egress from the bone marrow to the blood and infiltrate the myocardium hours after AMI [9,10]. Different studies have suggested that an exacerbated and prolonged inflammatory reaction causes irreparable damage which could be responsible for the progression of LVAR [11,12]
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