Potential role of circulating exosome miRNAs in left ventricular remodeling of patients with ST-segment elevation myocardial infarction

Abstract

Background Left ventricular remodeling (LVR) in patients with ST-segment elevation myocardial infarction (STEMI) may lead to poor prognosis in which circulating exosome miRNAs play a critical role. The aim of the present study is to identify specific exosome miRNAs for LVR in patients with STEMI. Method Plasma exosome miRNAs were assessed in 20 patients (90% male, mean age of 66.95±1.65 years) 3–6 months after STEMI and 24 healthy individuals (83% male, mean age of 33.2±0.93 years) by using qPCR. Of the 20 patients, 8 had post-STEMI LVR according to echocardiographic evaluation, and the others did not. Clinical biochemical data including total cholesterol, HDL-C, LDL-C, LDH and NT-pro-BNP were collected from the patients with STEMI at same time as exosome miRNAs assessment. Specific exosome miRNAs for LVR were identified by using qPCR. Correlations between the dysregulated exosome miRNAs and the clinical biochemical parameters in patients with STEMI were analyzed using spearman correlation test. Results Five exosome miRNAs including hsa-miR-181a-3p (p<0.05, fold change = 0.59), let-7d-3p (p=0.01, fold change = 0.51), hsa-miR-224-5p (p<0.01, fold change = 0.11), hsa-miR-23a-3p (p<0.01, fold change = 1.42) and miR-874-3p (p<0.01, fold change = 0.48) were dysregulated in the post-STEMI patients comparing with the healthy individuals. Among them, the exosome miR-181a-3p (p=0.01, fold change = 0.09) and let-7d-3p (p=0.01, fold change = 0.16) were significantly lower expressed in patients with LVR compared to those without (Figure 1). There was no significant difference in expression of the other three miRNAs between patients with and without LVR. Exosome hsa-miR-874-3p positively associated with LDH (p<0.01, r=0.50) in all the patients with STEMI. In vitro cell culture confirmed that the miR-874-3p mimics upregulated expression of apoptosis related gene BMF (p<0.05, fold change = 1.7) in cardiomyocyte. Exosome hsa-miR-23a-3p and hsa-miR-224-5p positively correlated with both HDL-C (p<0.01, r=0.61; p=0.02, r=0.50) and LDL-C (p=0.02, r=0.50; p<0.05, r=0.52) in all patients with STEMI. No correlation between the dysregulated exosome miRNAs and cholesterol or NT-ProBNP was observed (Figure 2). Conclusions Circulating exosome miR-181a-3p and let-7d-3p might play a potential role in LVR in patients 3–6 months after STEMI. Exosome hsa-miR-874-3p might be associated with cardiomyocyte injury. Hsa-miR-23a-3p and hsa-miR-224-5p demonstrated an activity in regulation of lipid metabolism and biosynthesis in patients with STEMI. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): This work was supported by grants from the 3×3 Clinical Scientist Fund of Sun Yat-sen Memorial Hospital