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Influence of Pyroptosis Induced by NOD-Like Receptor Pyrin Domain-Containing 3 Inflammasomes on Viral Myocarditis in
Huang Huang1, Jiwen Lou2, Wenhao Chen2
1Science of Prescription, Academy of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan, People's Republic of China.
Insights
Pyroptosis, driven by NLRP3 inflammasomes, is key in pediatric viral myocarditis (VMC). Combined gene and protein analysis of pyroptosis markers offers a more accurate diagnostic approach for VMC.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Viral myocarditis (VMC) is a primary cause of heart failure in children.
- Pyroptosis, a programmed cell death pathway involving NLRP3 inflammasomes, contributes to myocardial injury.
- The diagnostic value of combined gene and protein expression in VMC is not well-established.
Purpose of the Study:
- To investigate the role of NLRP3 inflammasome-mediated pyroptosis in pediatric VMC.
- To evaluate if integrated gene and protein profiling enhances diagnostic prediction for VMC.
Main Methods:
- 100 children were studied: 50 with VMC and 50 with dilated cardiomyopathy.
- Myocardial tissues were analyzed for protein and gene expression of NLRP3, Caspase-1, Gasdermin D (GSDMD), and IL-1β.
- Techniques included ELISA, immunohistochemistry, RT-PCR, and Western blotting.
Main Results:
- Children with VMC showed significantly higher protein and gene expression of NLRP3, Caspase-1, GSDMD, and IL-1β compared to controls.
- Expression levels of these markers positively correlated with VMC presence.
- Combined gene and protein analysis yielded a higher diagnostic accuracy (AUC) than individual markers.
Conclusions:
- NLRP3 inflammasome-mediated pyroptosis is integral to pediatric VMC pathogenesis.
- Combined gene and protein assessment offers a reliable method for early VMC diagnosis and risk stratification.
- Inflammasome-related biomarkers show potential as therapeutic targets for VMC.
Purpose:
Viral myocarditis (VMC) is a leading cause of heart failure and dilated cardiomyopathy in children. Pyroptosis, an inflammatory form of programmed cell death mediated by NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasomes, has been implicated in myocardial injury. However, the diagnostic significance of combined gene and protein expression analysis remains unclear. This study aimed to clarify the role of NLRP3 inflammasome-mediated pyroptosis in pediatric VMC and assess whether integrated gene-protein profiling could enhance diagnostic prediction.
Patients And Methods:
A total of 100 children were enrolled, including a case group (n=50, children with viral myocarditis hospitalized between September 2023 and September 2024) and a control group (n=50, patients with dilated cardiomyopathy during the same time period). The expression levels of proteins interleukin-1β (IL-1β), NLRP3, Gasdermin D (GSDMD) and Caspase-1, and genes GSDMD, NLRP3, and Caspase-1 in myocardial tissues were measured through enzyme-linked immunosorbent assay, immunohistochemistry, real-time polymerase chain reaction, and Western blotting.
Results:
No significant differences were found between the two groups regarding age, gender, or clinical history (P>0.05). Compared with the control group, the case group exhibited significantly higher expression of NLRP3, Caspase-1, GSDMD, and IL-1β at both protein and gene levels (P<0.05). Correlation analyses confirmed that these markers were positively associated with the presence of VMC. (P<0.05). Receiver operating characteristic (ROC) analysis revealed that the combined detection of gene and protein expression achieved a higher area under the curve (AUC) than any single indicator, demonstrating superior diagnostic accuracy.
Conclusion:
NLRP3 inflammasome-mediated pyroptosis plays a crucial role in the pathogenesis of viral myocarditis in children. The combined assessment of gene and protein expression levels provides a novel and more reliable approach for early diagnosis and risk evaluation of pediatric VMC, highlighting the potential of inflammasome-related biomarkers as therapeutic targets.
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