講演情報

[II-TKIS-OR-4]Regulatory mechanism of postnatal development of mouse cardiac lymphatic vessels

Soyoka Fujita1, Seina Nakayama1, Sota Torii3, Kazuaki Maruyama1, Kyoko-Imanaka Yoshida2 (1.Deparment of Pathology and Matrix biology, Mie University, 2.Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 3.Suzuka General Hospital)
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キーワード:

Myocarditis、Lymphatic vesseels、Prox1

BackgroundMyocarditis is an inflammatory heart disease in adolescents and young adults that can cause severe heart failure. It is often considered an autoimmune disease triggered by viral infection, yet its mechanisms remain poorly understood. We have studied cardiac lymphatic vessels and their roles in inflammation resolution (Maruyama et al., iScience, 2021; Nakanishi, Fujita et al., Cardiovascular Research, 2026). However, the significance of postnatal cardiac lymphatic maturation remains unclear.
ObjectiveTo define how postnatal cardiac lymphatic development is coordinated with cardiac immune function and how this influences myocarditis.
MethodsPostnatal cardiac lymphatic development was examined in mouse hearts by immunostaining. Myocarditis was induced in mice with endothelial cell-specific deletion of Prox1, followed by analysis of endothelial transcriptional changes.
ResultsCardiac lymphatics rapidly grew during postnatal weeks 2-3 and progressively covered the heart. scRNA-seq revealed endothelial cell-cycle activity until weeks 2-3, followed by immune-related gene expression thereafter. Prox1 deletion impaired lymphatic development, disrupted T-cell and macrophage homeostasis, and exacerbated myocarditis.
ConclusionsPostnatal cardiac lymphatics undergo both structural and functional maturation, acquiring immune-regulatory functions. Our findings suggest a developmental transition from growth to immune regulation that contributes to cardiac stability and indicate that enhancing lymphatic maturation may represent a therapeutic strategy for pediatric myocarditis.