Recently, the supra-normal left ventricular ejection fraction (snLVEF) has been proposed, based on extensive datasets indicating increased all-cause mortality in individuals with an LVEF exceeding 65%. However, the implications of an LVEF > 65% in the context of acute coronary syndrome (ACS) remain underexplored.The aim of the present study was to investigate the correlation between supra-normal left ventricular ejection fraction (snLVEF) and major adverse cardiovascular events (MACE) in patients with ACS.Methods: A total of 874 ACS patients (560 men, mean age 59.5 ± 10.0; 314 women, mean age 61.5 ± 8.9) who underwent their first coronary angiography during the period from March 2013 to October 2015 were divided into 2 groups: normal LVEF (nLVEF) (55% ≤ EF ≤ 65%) and snLVEF (EF > 65%), according to their echocardiography results. The patients were evaluated for MACE after surgery by collecting clinical data and long-term follow-up data. This correlation was further analyzed by Kaplan-Meier analysis and Cox regression analysis.The follow-up data revealed a significantly higher incidence of MACE among snLVEF patients compared to the nLVEF group (15.6% versus 7.4%; P = 0.020). This heightened risk persisted even after adjustment for multiple variables, indicating a strong association between snLVEF and increased MACE risk (HR: 2.346; 95% CI: 1.196-4.602; P = 0.013).SnLVEF was independently associated with poor prognosis after ACS. Enhanced management strategies for snLVEF patients could potentially reduce the incidence of MACE in ACS patients.

Atherosclerosis is a lipid-driven chronic inflammatory disease. Endothelial dysfunction caused by oxidized low-density lipoprotein (ox-LDL) is the initiating factor of atherosclerosis. Although much work has been done on the anti-atherosclerotic effects of interleukin-37(IL-37), the exact mechanism is still not fully explained. The aim of this study was to investigate whether IL-37 attenuates atherosclerosis by protecting endothelial cells, and to confirm whether autophagy plays a role in this effect. Human umbilical vein endothelial cells (HUVECs) treated with ox-LDL were used to establish endothelial dysfunction model. Cell viability was determined by cell counting Kit-8. Flow cytometry and TUNEL were used to detect the apoptosis. IL-1β and TNF-α were detected by ELISA. Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammatory components and autophagy-related proteins were assessed by western blot. Transmission electron microscopy and RFP-GFP-LC3 tandem fluorescence detection were performed to further verify the autophagy level. 3-methyladenine (3-MA) was added to investigate whether autophagy was involved in the anti-endothelial dysfunction effect of IL-37. We observed IL-37 potently alleviated ox-LDL-induced impairment of cell viability, NLRP3 activation of inflammasome, ROS production and apoptosis. Simultaneously, IL-37 could activate autophagy in endothelial cells, which is manifested as up-regulation of LC3II/LC3I, down-regulation of p62 and increased autophagosomes. Furthermore, the addition of autophagy inhibitor 3-MA dramatically reversed the promotion of autophagy and the protective effect of IL-37 on endothelial injury. Our data illustrates that IL-37 alleviated ox-LDL-induced inflammation, oxidative stress, and apoptosis in HUVECs by enhancing autophagy. The current study provides new insights and promising therapeutic strategies for atherosclerosis.

Atherosclerosis is a lipid-driven chronic inflammatory disease. Endothelial dysfunction is the initiating factor of atherosclerosis. Although much work has been done on the antiatherosclerotic effects of interleukin-37 (IL-37), the exact mechanism is still not fully understood. The aim of this study was to investigate whether IL-37 at-tenuates atherosclerosis by protecting endothelial cells and to confirm whether autophagy plays a role in this effect. In apolipoprotein E knockout (ApoE-/-) mice fed with a high fat diet, IL-37 treatment significantly attenuated progression of atherosclerotic plaques, reduced endothelial cell apoptosis and inflammasome acti-vation. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish an endothelial dysfunction model. We observed that IL-37 alleviated ox-LDL-induced endothelial cell inflammation and dysfunction, as evidenced by decreased nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation, ROS production, apoptosis rate and secretion of inflamma-tory cytokines IL-1 beta and TNF-alpha. Furthermore, IL-37 could activate autophagy in endothelial cells, which is characterized by the upregulation of LC3II/LC3I, the downregulation of p62 and an increase in autophagosomes. The autophagy inhibitor 3-Methyladenine (3-MA) dramatically reversed the promotion of autophagy and the protective effect of IL-37 against endothelial injury. Our data illustrate that IL-37 alleviated inflammation and apoptosis of atherosclerotic endothelial cells by enhancing autophagy. The current study provides new insights and promising therapeutic strategies for atherosclerosis.

OBJECTIVE:To investigate whether interleukin-37 (IL-37) could directly inhibit the formation of neutrophil extracellular traps (NETs) in the early stage of acute viral myocarditis (VMC) and its potential mechanisms of action.METHODS:Acute VMC was induced by intraperitoneally injecting coxsackievirus B3 (CVB3)(103 TCID50) in mice on day 0. Mice were injected with AAV9-IL-37 or AAV9-NC through the caudal vein 1 week before intraperitoneal administration of CVB3. DNASE1 (50ug per mouse) was administered on days 0 to 7 to investigate the role of NETs formation during acute VMC. The severity of myocardial inflammation was evaluated by observing the general condition of mice and detecting cardiac histopathology. Moreover, neutrophils isolated from healthy human peripheral blood were stimulated by phorbol myristate acetate (PMA 100 nM) and treated with IL-37 (0.1 ng/ml) or BAY11-7082(2.5uM) in vitro. The production of NETs was detected by immunofluorescence labeled MPO and DNA. The expression of related proteins (IκBα, P-IκBα, NFκb, P-NFκb) was detected by Western blot.RESULTS:The results showed that, like DNASE1, IL-37 alleviates the symptoms in acute VMC induced by CVB3, reduces inflammatory cell infiltration, improves cardiac function, and inhibits the formation of NETs in the myocardium. Besides, both IL-37 and DNASE1 could effectively inhibit the activation of NFκb /IκBα. In the isolated peripheral blood neutrophils, the inhibitory effect of IL-37 on the formation of NETs and the activation of NFκb /IκBα was further confirmed.CONCLUSION:IL-37 has a protective effect on VMC by reducing the infiltration of inflammatory cells and inhibiting the formation of NETs at an early phase.