Background:Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOSs) for the synthesis of nitric oxide (NO). BH4 therapy can reverse the disease-related redox disequilibrium observed with BH4 deficiency. However, whether BH4 exerts a protective effect against radiation-induced damage to cardiomyocytes remains unknown.Methods:Clonogenic assays were performed to determine the effects of X-ray on H9c2 cells with or without BH4 treatment. The contents of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) in H9c2 cells were measured to investigate oxidative stress levels. The cell cycle undergoing radiation with or without BH4 treatment was detected using flow cytometry. The expression levels of proteins in the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/P53 signaling pathway, inducible NOS (iNOS), and endothelial NOS (eNOS) were examined using Western blotting.Results:X-ray radiation significantly inhibited the growth of H9c2 cells in a dose-dependent manner, whereas BH4 treatment significantly reduced the X-ray radiation-induced growth inhibition (control group vs. X-ray groups, respectively, P < 0.01). X-ray radiation induced LDH release, apoptosis, and G0/G1 peak accumulation, significantly increasing the level of MDA and the production of NO, and decreased the level of SOD (control group vs. X-ray groups, respectively, P < 0.05 or P < 0.01). By contrast, BH4 treatment can significantly reverse these processes (BH4 treatment groups vs. X-ray groups, P < 0.05 or P < 0.01). BH4 reversed the X-ray radiation-induced expression alterations of apoptosis-related molecules, including B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein, and caspase-3, and molecules of the PI3K/Akt/P53 signaling pathway. BH4 enhanced the production of NO in 2 Gy and 4 Gy radiated groups by upregulating eNOS protein expression and downregulating iNOS protein expression.Conclusions:BH4 treatment can protect against X-ray-induced cardiomyocyte injury, possibly by recoupling eNOS rather than iNOS. BH4 treatment also decreased oxidative stress in radiated H9c2 cells.
BackgroundPolymorphisms of the endothelial nitric oxide synthase (eNOS) gene are reportedly associated with myocardial infarction (MI) risk. However, definitive evidence of this association is lacking. In this study, we investigated the potential association of eNOS gene polymorphisms with MI risk by conducting a meta-analysis of studies evaluating this association.Material/MethodsPubMed, Web of Knowledge, ScienceDirect, China National Knowledge Infrastructure (CNKI), WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP) were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated to evaluate the association of eNOS gene T-786C and 4b4a polymorphisms with MI risk.ResultsFifteen studies with 8,067 controls and 4,923 MI cases were included in the final meta-analysis. In the overall analysis, T-786C (rs2070744) polymorphism was associated with MI risk (p<0.05, OR=1.69, 95% CI: 1.53–1.86 for T vs. C; p<0.05, OR=2.76, 95% CI: 2.03–3.75 for TT vs. CC; p<0.05, OR=1.74, 95% CI 1.56–1.95 for TT vs. (CT + CC); p<0.05, OR=2.43, 95% CI: 1.79–3.30 for (CT + TT) vs. CC). In addition, a significant association between 4b4a VNTR polymorphism and MI risk was observed. On sub-group analyses by ethnicity, a significant increase in MI risk was observed separately for Asian and Caucasian populations for T-786C polymorphism, but not for the 4b4a polymorphism.ConclusionsIn this meta-analysis, T-786C polymorphism of the eNOS gene was associated with the risk of MI, especially in the Asian populations.
Background Atrial fibrillation (AF) is associated with impaired quality of life, anxiety and depression. Compared with the use of antiarrhythmic drugs, the quality of life of patients with AF after catheter ablation (CA) has significantly improved, but the research on the role of family function, anxiety and depression is relatively limited. This study aims to determine how different treatment strategies lead to changes in the quality of life, family function, anxiety and depression of patients with symptomatic paroxysmal AF, and to explore the influencing factors of clinically significant changes in the quality of life of patients with symptomatic paroxysmal AF. Methods The patients with AF diagnosed and treated in the Department of Cardiology of the Second Hospital of Lanzhou University from January 1, 2021 to May 1, 2022 were selected as the research objects in strict accordance with the inclusive criteria. Questionnaires were designed to collect general information about the patients; the Atrial Fibrillation Effect on Quality-of-life (AFEQT), the Family Adaptation, Partnership, Growth, Affection, Resolve (APGAR), the Generalized Anxiety Disorder 7 (GAD-7) and the Patient Health Questionnaire 9 (PHQ-9) were used to assess the patients’ quality of life, family function, anxiety and depression levels at baseline and after 6 months of clinical follow-up, respectively.Construction of a logistic regression model to analyze the factors influencing clinically meaningful changes in overall quality of life in patients with symptomatic paroxysmal AF. Results 188 patients with AF were included in this study, including 87 cases in the CA group and 101 cases in the antiarrhythmic drug (AAD) group. Compared with the AAD group, patients in the CA group had significantly better quality of life (60.81±6.63 vs 76.30±6.86), family function (5.67±2.38 vs 8.01±2.13), anxiety (6.36±2.62 vs 4.98±2.58) and depression levels (5.39±2.89 vs 4.45±3.52) significantly improved (all P < 0.05). Analysis of factors influencing clinically meaningful changes in overall quality of life in patients with symptomatic paroxysmal AF revealed, a clinically meaningful increase in overall quality of life in patients who underwent CA (OR=233.20, 95% CI: 58.51-929.43, P=0.001), and a clinically meaningful decrease in overall quality of life in patients with AF of more than 5 years duration (OR=3.32, 95% CI: 1.13-9.74, P = 0.029) had a clinically meaningful decrease in overall quality of life. Conclusions CA is effective in improving quality of life, family function, anxiety, and depressive symptoms in patients with symptomatic paroxysmal AF compared with AAD, and patients undergoing CA are more likely to experience clinically meaningful increases in overall quality of life, primarily due to relief of AF symptoms and reduced disease burden.
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