Background: Viral myocarditis (VMC) is a common inflammatory cardiovascular disease with unclear mechanisms, which mainly affects children and adolescents. Apoptosis is the key to CVB3-induced myocarditis, and blocking this process may be beneficial to the therapy of VMC. Hence, this study aimed to explore the protective function of STAT3 on cardiomyocyte apoptosis of VMC and its underlying mechanisms.Methods and Results: In this research, we confirmed that STAT3 was significantly activated in both animal and cell models of VMC. To further clarify what role did STAT3 play in VMC, AG490, an inhibitor of STAT3, was used to suppress p-STAT3. Our results demonstrated that decreased expression of p-STAT3 caused by AG490 significantly aggravated severity of VMC with elevated myocardial inflammation, deteriorative ventricular systolic function and increased mortality. It suggested that STAT3 plays a protective role in VMC. To further identify the anti-apoptosis impact that activated STAT3 made, we constructed lentivirus to regulate the expression of STAT3 in NMCs. We found that up-regulated activated STAT3 attenuated cardiomyocyte apoptosis, but down-regulated one aggravated that, which verified activated STAT3 played an anti-apoptosis role in VMC. Following that, we explored what elements are involved in the anti-apoptotic mechanism of activated STAT3 by using survivin inhibitor YM155. The result showed the anti-apoptotic effect of activated STAT3 does not work in the case of survivin inhibition.Conclusion: Our findings demonstrated STAT3 by targeting survivin alleviated cardiomyocyte apoptosis in CVB3-induced myocarditis.
Background and Purpose. Docosahexaenoic acid (DHA) is a type of polyunsaturated fatty acid enriched in cod liver oil and seaweed. It is necessary for the human body and has important functions, such as antioxidation and antiatherosclerosis activities. Long-term oral administration of DHA or the use of DHA at the initial stage of ischemia can increase the level of autophagy and exert a protective effect on neurological functions related to cerebral infarction. However, the effect of DHA on myocardial injury and cardiac insufficiency after myocardial infarction (MI) is unknown. This study was aimed at exploring whether DHA plays a protective role in AMI and its specific molecular mechanism. Experimental Method. In vitro cardiomyocyte hypoxia and in vivo MI injury models were used to determine the role of DHA in MI. Hypoxic injury induced damage in cultured neonatal mouse cardiomyocytes (NMCs). The C57BL/6J mouse MI model was established by permanent ligation of the left anterior descending branch. Main Results. DHA improved the cardiomyocyte viability of NMCs induced by hypoxia injury and reduced cell necrosis. DHA reduced infarct size, improved heart function, and reduced the degree of myocardial fibrosis in mice after MI. In addition, DHA enhanced autophagy flux and reduced apoptosis in vitro and in vivo. In addition, we found that chloroquine, an autophagy inhibitor, blocked the protective effect of DHA on cardiomyocyte apoptosis and cardiac dysfunction, indicating that DHA exerts cardioprotective effects in part by promoting autophagy flux. We also observed that DHA enhanced autophagy flux by activating the AMPK/mTOR signaling pathway. Conclusions and Significance. In conclusion, our findings indicate for the first time that DHA improves MI-induced cardiac dysfunction by promoting AMPK/mTOR-mediated autophagic flux.
Coronary artery lesions (CALs) are severe complications of Kawasaki disease (KD), resulting in stenosis and thrombogenesis. Metabolomic profiling of patients’ plasma could assist in elucidating the pathogenesis of CALs and identifying diagnostic biomarkers, which are imperative for clinical treatment. The metabolic profiles between KD patients with CALs and without CALs (non-coronary artery lesion, or NCAL, group) indicated the most significantly differentially expressed metabolite, palmitic acid (PA), showed the most massive fold change at 9.879. Furthermore, PA was proven to aggravate endothelial cellular senescence by increasing the generation of reactive oxygen species (ROS) in KD, and those two phenotypes were confirmed to be enriched among the differentially expressed genes between KD and normal samples from GEO datasets. Collectively, our findings indicate that cellular senescence may be one of the mechanisms of vascular endothelial damage in KD. PA may be a biomarker and potential therapeutic target for predicting the occurrence of CALs in KD patients. All things considered, our findings confirm that plasma metabolomics was able to identify promising biomarkers and potential pathogenesis mechanisms in KD. To conclude, Palmitic acid could be a novel target in future studies of CALs in patients with KD.
Background: Transcatheter closure is an important treatment for patent ductus arteriosus (PDA) complicated with moderate and severe pulmonary arterial hypertension (PAH). This report presents our experience with transcatheter closure of PDA complicated with moderate and severe PAH.Methods: The 49 cases of PDA complicated with moderate and severe PAH were collected in the Second Affiliated Hospital and Yuying Children's Hospital from January 2014 to December 2019 with transcatheter closure of PDA and follow-up. All patients were invited for transthoracic echocardiography, electrocardiogram, and thoracic radiography check-up.Results: Device implantation was successful in 48 of 49 patients (98.0%). Among them, 30 cases were in the PAH after defect correction (CD) group, and 19 examples were in the Non-PAH after defect correction (NCD) group. Pulmonary systolic pressure, left atrial diameter, and left ventricular end-diastolic diameter immediately after interventional therapy and 6 months later were lower than the pre-operative levels (p < 0.05). The incidence of the immediate residual shunt (RS) in this study was 34.9%, most of which were minimal amount shunt. RS disappeared in all patients within 1 year of therapy. Four patients had thrombocytopenia and one patient had left pulmonary artery stenosis. No other serious adverse event occurred during the follow-up period. The pressure gradient tricuspid valve regurgitation (PGTI) and the right heart catheterization (RHC) consistency points were 93.75% (15/16) and were within the 95% consistency limit by the Bland-Altman method. The Logistic regression analysis concluded that the pre-operative Pp/Ps and the narrowest diameter of PDA are risk factors for post-operative PAH (p < 0.05). The cut-off point of the pre-operative Pp/Ps and the narrowest diameter of PDA were calculated to be 0.595 and 4.75 mm, respectively.Conclusion: Interventional occlusion in children with PDA complicated with moderate and severe PAH is safe, effective, and has few complications. Targeted drug therapy has a good clinical effect. The narrowest diameter of PDA and the pre-operative Pp/Ps may be one of the risk factors of residual PAH after interventional therapy.
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