MicroRNA-155-5p in serum derived-exosomes promotes ischaemia-reperfusion injury by reducing CypD ubiquitination by NEDD4.

AIMS: Recovery of blood flow is a therapeutic approach for myocardial infarction but paradoxically induces injury to the myocardium. Exosomes (exos) are pivotal mediators for intercellular communication that can be released by different cells and are involved in cardiovascular diseases. This study aimed to explore the possible effects and mechanisms of miR-155-5p loaded by serum-derived exos in myocardial infarction reperfusion injury (MIRI). METHODS AND RESULTS: Exos were isolated from mouse serum after induction of ischaemia reperfusion (I/R) and injected into I/R-treated mice to assess cardiac function, infarction size, and cardiomyocyte apoptosis. Primary cardiomyocytes were transfected with miR-155-5p inhibitor before treatment with oxygen-glucose deprivation and re-oxygenation (OGD/R) and exos derived from the serum of I/R-treated mice (I/R-Exos), in which Bcl-2, Bax, and cleaved-caspase-3 levels were detected. The interactions among miR-155-5p, NEDD4, and CypD were evaluated. miR-155-5p level was evidently increased in I/R-Exos than in exos from the serum of sham-operated mice (P < 0.05). In comparison with the I/R group, the I/R-Exos + I/R group had increased infarct size, elevated miR-155-5p expression, and boosted apoptotic rate in mouse myocardium (P < 0.05). In mice treated with I/R-Exos and I/R, miR-155-5p inhibition reduced cardiac infarct size and apoptosis (P < 0.05). NEDD4 was a target gene of miR-155-5p and promoted CypD ubiquitination. Cardiomyocyte apoptosis was markedly increased in the miR-155-5p inhibitor + shNEDD4 + OGD/R group versus the miR-155-5p inhibitor + OGD/R group (P < 0.05), but decreased in the miR-155-5p inhibitor + shNEDD4 + shCypD + OGD/R group than in the miR-155-5p inhibitor + shNEDD4 + OGD/R group (P < 0.05). CONCLUSIONS: miR-155-5p in I/R-Exos may facilitate MIRI by inhibiting CypD ubiquitination via targeting NEDD4.

A Nomogram model for predicting the occurrence of no-reflow phenomenon after percutaneous coronary intervention using the lncRNA TUG1/miR-30e/NPPB biomarkers.

Background: Studies have shown that percutaneous coronary intervention (PCI) is considered as the essential therapeutic strategy for the patients with ST-segment elevation myocardial infarction (STEMI). However; no-reflow could still occur in a few patients after PCI. Studies have reported that biomarkers related to no-reflow pathogenetic components could play a prognostic role in the prediction phenomenon. Hence, this study explored the establishment of nomogram model for predicting the occurrence of no-reflow phenomenon after PCI using the lncRNA TUG1/miR-30e/NPPB biomarkers in patients with STEMI after PCI. Methods: In this observational study, a total of 76 STEMI patients who underwent emergency PCI between January 2018 and December 2021were included. The patients after PCI, were divided into reflow (n=44) and no-reflow groups (n=32). The demographic, environmental and clinical risk factors were assessed and analysed between the groups. Quantitative RT-PCR was used to detect TUG1, miR-30e, and NPPB messenger RNA (mRNA) expression levels in the plasma of patients after PCI. Bioinformatic methods were used to predict the interaction of the plasma TUG1/miR-30e/NPPB axis. The risk factors in the no-reflow group were screened using a logistic-regression analysis, and a nomogram prediction model was constructed and validated. Subsequently, a gene set enrichment analysis revealed the function of lncRNA TUG1. Results: Plasma lncRNA TUG1 and NPPB were more highly expressed and miR-30e was more lowly expressed in the no-reflow group than the normal-reflow group (P<0.001). A negative correlation was observed between lncRNA TUG1 and miR-30e, and between miR-30e and NPPB. However, a positive correlation was observed between lncRNA TUG1 and NPPB mRNA. The bioinformatics analysis predicted multiple binding sites on the lncRNA TUG1 and miR-30e. LncRNA TUG1 [odds ratio (OR): 0.163, 95% confidence interval (CI): 0.021-0.944] and hs-CRP (OR: 2.151, 95% CI: 1.536-3.974) found to be as independent predictors. The C-index of this prediction model was 0.982 (95% CI: 0.956-1.000). Conclusions: TUG1 could function as an effective biomarker for no-reflow among patients with STEMI after PCT and the proposed nomogram may provide information for individualized treatment in patients with STEMI.