Article Dans Une Revue EMBO Molecular Medicine Année : 2025

Molecular determinants of cardiac lymphatic dysfunction in a chronic pressure-overload model

Coraline Heron
Theo Lemarcis
Océane Laguerre
Bénjamin Bourgeois
Corentin Thuilliez
Chloé Valentin
  • Fonction : Auteur
Anais Dumesnil
  • Fonction : Auteur
Manon Valet
  • Fonction : Auteur
Damien Schapman
  • Fonction : Auteur
Gaetan Riou
  • Fonction : Auteur
Sophie Candon
Alma Zernecke
Virginie Tardif

Résumé

Abstract Cardiac lymphatic alterations and insufficient lymphatic drainage have been found in cardiovascular diseases (CVDs). To unravel the mechanisms underlying lymphatic dysfunction, we applied single-cell (sc) analyses in murine heart failure (HF) models. Transaortic constriction (TAC) in C57BL/6J and BALB/c mice modeled chronic pressure -overload-induced cardiac hypertrophy and HF, respectively. Cardiac lymphatic (LEC) and blood vascular endothelial cells (BEC) were analyzed by scRNAseq, and targets validated by immunohistochemistry and human LEC cultures. While LEC profiles were comparable between strains in healthy mice, we found expansion of lymphatic capillaries and loss of valves post-TAC only in BALB/c. Differentially expressed gene (DEG) analysis revealed a reduction post-TAC only in BALB/c of lymphatic junctional components. Conversely, LEC expression of immune cell cross-talk mediators was mostly preserved post-TAC. Interestingly, around 35% of DEGs identified in cardiac LECs post-TAC were similarly altered in interleukin (IL)1β-stimulated human LECs. In conclusion, loss of lymphatic valves and dysregulated lymphatic barrier may underlie poor drainage capacity during pressure-overload-induced HF, despite potent lymphangiogenesis and preserved LEC immune attraction. Our work provides tractable targets to restore lymphatic health in CVDs.

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Coraline Heron, Theo Lemarcis, Océane Laguerre, Bénjamin Bourgeois, Corentin Thuilliez, et al.. Molecular determinants of cardiac lymphatic dysfunction in a chronic pressure-overload model. EMBO Molecular Medicine, 2025, 18 (1), pp.325-355. ⟨10.1038/s44321-025-00345-w⟩. ⟨hal-05485217⟩
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