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Background: The Nod-Like-Receptor-Protein-3 (NLRP3) inflammasome and the Interleukin-6 (IL-6) pathways are central mechanisms of the inflammatory response in myocardial reperfusion injury. Expanding our knowledge about the inflammasome signaling axis is important to improve treatment options. In a cross-sectional study, we aimed to study presence, localization, and genetic expression of inflammasome- and IL-6- signaling-related proteins in coronary thrombi and circulating leukocytes from ST-elevation myocardial infarction (STEMI) patients, with relation to myocardial injury and time from symptoms to PCI., Methods: Intracoronary thrombi were aspirated from 33 STEMI patients. Blood samples were drawn. mRNA of Toll-Like-Receptor-4 (TLR4), NLRP3, caspase 1, Interleukin-1 β (IL1- β ), Interleukin-18 (IL-18), IL-6, IL-6-receptor (IL-6R), and glycoprotein 130 (gp130) were isolated from thrombi and circulating leukocytes and relatively quantified by RT-PCR. A part of each thrombus was embedded in paraffin for histology and immunohistochemistry analyses., Results: Genes encoding the 8 markers were present in 76-100% of thrombi. Expression of TLR4 in thrombi significantly correlated to troponin T ( r = 0.455, p = 0.013), as did NLRP3 ( r = 0.468, p = 0.024). Troponin T correlated with expression in circulating leukocytes of TLR4 ( r = 0.438, p = 0.011), NLRP3 ( r = 0.420, p = 0.0149), and IL-1 β ( r = 0.394, p = 0.023). IL-6R expression in thrombi correlated significantly to troponin T ( r = 0.434, p = 0.019), whereas gp130 was inversely correlated ( r = -0.398, p = 0.050). IL-6 in circulating leukocytes correlated inversely to troponin T ( r = -0.421, p = 0.015). There were no significant correlations between genes expressed in thrombi and time from symptom to PCI., Conclusions: The inflammasome signaling pathway was actively regulated in coronary thrombi and in circulating leukocytes from patients with STEMI, in association with myocardial damage measured by troponin T. This supports the strategy of medically targeting this pathway in treating myocardial infarction and contributes to sort out optimal timing and targets for anti-inflammatory treatment. The study is registered at clinicaltrials.gov with identification number NCT02746822., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Jostein Nordeng et al.)

The aim of the study was to evaluate the clinical significance of microRNA-375 in acute myocardial infarction patients and its mimic action in hypoxia/reoxygenation- (H/R-) induced ventricular cardiomyocyte H9c2 injury. In the current study, 90 ST-elevated acute MI patients (STEMI), 75 non-ST-elevated acute MI patients (NSTEMI), 90 healthy subjects, 14 weeks old mice, and ventricular cardiomyocyte H9c2 were included. The expressions of plasma microRNA-375 in patients with STEMI and NSTEMI and AMI mouse models were remarkably decreased than in controls ( P < 0.001). The areas under the curve (AUC) of plasma microRNA-375 were revealed 0.939 in STEMI and 0.935 in NSTEMI subjects. Moreover, microRNA-375 levels in H/R-exposed cardiac H9c2 cells were evidently downregulated and significantly increased apoptosis rate and caspase-3 activity levels, while overexpression of miR-375 remarkably reduced apoptosis percentage and caspase-3 levels as compared with normal cells. Furthermore, this study also demonstrated that Nemo-like kinase (NLK), NLK mRNA, and protein expression levels were significantly downregulated in H/R-injured H9c2 cells, on the contrary, H9c2 cells transfected with mimic-miR-375 greatly upregulated NLK mRNA and protein expression. Plasma microRNA-375 may serve as an essential clinical biomarker for diagnosis of early-stage AMI. Mimic expression of miR-375 significantly prevented H/R-induced cardiomyocyte injury by decreasing caspase-3 activity through upregulation of the NLK gene, recommended as a new therapeutic option for AMI patient., Competing Interests: There is no conflict of interest in this article., (Copyright © 2020 Md Sayed Ali Sheikh.)

Background: The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients., Methods and Results: In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p ≤ 0.02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p < 0.03). Moreover, they had lower LVEF acutely and after 4 months, and larger change in LVEDVi (all p ≤ 0.014). High day 1 dsDNA levels also associated with risk of having a large infarct size (>75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p < 0.021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p = 0.012). No such observations were encountered for MPO-DNA., Conclusions: High day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008))., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 Ragnhild Helseth et al.)

Purpose: To investigate the association of galectin-3 (Gal-3) and soluble ST2 (sST2) and their follow-up changes with the development of heart failure (HF) and echocardiographic parameters of HF (ejection fraction, atrial and ventricular size, left ventricular hypertrophy, e', and E/e') in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI)., Methods: A prospective, observational study, BIOSTRAT (Biomarkers for Risk Stratification After STEMI), enrolled 117 patients between October 2014 and April 2017. Gal-3 and sST2 serum collection and echocardiography were performed twice (during index hospitalization and on a control visit at one-year follow-up). The primary endpoint was HF onset at one-year follow-up. Secondary assessments included associations of biomarker concentration with echocardiographic indices of systolic and diastolic dysfunction at baseline and at one year., Results: Mean baseline concentrations of Gal-3 and sST2 (7.5 and 26.4 ng/mL, respectively) were significantly increased at one-year follow-up (8.5 ng/mL and p < 0.001 and 31.4 ng/mL and p = 0.001, respectively). Patients who reached the primary endpoint (50 patients (48%)) had significantly higher baseline concentrations of both biomarkers and a higher Gal-3 level at one year compared to patients who did not. Both Gal-3 and sST2 were predictors of the primary endpoint in univariate logistic regression analysis, but only Gal-3 remained significant in multivariate analysis. There was no clear association between both biomarkers and echocardiographic parameters., Conclusions: Baseline, but not one-year, changes of Gal-3 and sST2 concentrations may be useful for risk stratification after STEMI. However, only Gal-3 was the independent predictor of HF development at one-year observation. This trial is registered with NCT03735719., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 Agata Tymińska et al.)