Key result
PTX3 overexpression increases NLRP3 expression and macrophage migration vs LPS alone in cardiomyocytes.
Why the study?
To investigate the expression of PTX3 and NLRP3 in myocarditis and elucidate their roles and potential interplay in the pathogenesis of myocarditis.
p-value: p=0.0439
PTX3-mediated NLRP3 activation contributes to inflammatory responses and promotes macrophage migration in myocarditis, suggesting a potential therapeutic target.
PTX3 may drive NLRP3-mediated cardiomyocyte inflammation; leaves open its viability as a therapeutic target in myocarditis.
BACKGROUND: This study aims to investigate the expression of Pentraxin 3 (PTX3) and Nod-like receptor family pyrin domain-containing 3 (NLRP3) in myocarditis and to elucidate their roles and potential interplay in the pathogenesis of myocarditis. METHODS: Immunofluorescence staining was performed on myocardial autopsy specimens from deceased patients with severe myocarditis or severe trauma. H9C2 cardiomyocytes were divided into five groups: Control, Lipopolysaccharide (LPS), LPS + PTX3 overexpression, LPS + small interfering RNA targeting PTX3 (si-PTX3), and LPS + PTX3 overexpression + si-NLRP3. The expression levels of PTX3 and NLRP3 at the RNA level were quantified using quantitative real-time polymerase chain reaction (qPCR), while protein expression was assessed via western blot. The concentrations of interleukin-1β (IL-1β) and IL-18 were determined by enzyme-linked immunosorbent assay (ELISA). Macrophages migration was evaluated using Transwell assays. RESULTS: Immunofluorescence staining revealed co-localization and increased expression of PTX3 and NLRP3 in the myocardium of patients with severe myocarditis. In vitro experiments demonstrated that PTX3 enhanced the expression of NLRP3, IL-1β, and IL-18 in LPS-stimulated cardiomyocytes. Furthermore, PTX3 was shown to promote macrophage migration by regulating NLRP3 expression, as assessed by Transwell assays. CONCLUSION: Our findings suggest that PTX3-mediated NLRP3 activation contributes to inflammatory responses and promotes macrophage migration in myocarditis. This study provides a foundation for future investigations into PTX3-targeted therapies for myocarditis.
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Zhu et al. (2025) studied Myocarditis (n=2). PTX3 overexpression and siRNA knockdown vs. Lipopolysaccharide (LPS) alone or control siRNA was evaluated on Macrophage migration and expression of NLRP3, IL-1β, and IL-18 (p=0.0439). PTX3 overexpression significantly increased the expression of NLRP3 and downstream pro-inflammatory cytokines, and promoted macrophage migration compared to LPS alone in cardiomyocytes.
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