International journal of general medicine · 2025
Influence of Pyroptosis Induced by NOD-Like Receptor Pyrin Domain-Containing 3 Inflammasomes on Viral Myocarditis in Children.
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Rubinstein Jeremy D, Pham Giang, Sridharan Anusha, Khoury Ruby, Wang YunZu M, Hudda Zahra, Wilhelm Jamie, Lichtenstein Daniel A, Heyenbruch Daria, Cancelas Jose A, Davies Stella M, Lutzko Carolyn, Grimley Michael S
Аннотация
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.
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.