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Light microscopy reveals unexpected cardiac lymphatic remodelling

Light microscopy reveals unexpected cardiac lymphatic remodelling

AnnouncementNews from NodesPublications

Researchers from the University of Rouen (INSERM UMR1096, EnVI Laboratory), in collaboration with engineers from the Normandy microscopy platform PRIMACEN, both members of France-BioImaging, have identified genetic and cellular remodelling mechanisms of the cardiac lymphatic system in mice with cardiovascular diseases. This work provides new insights into the mechanisms underlying cardiac lymphatic dysfunction(1).

PRIMACEN, a platform at the heart of the project

As part of a research project dedicated to cardiovascular diseases, the PRIMACEN microscopy platform played a central role in the study of cardiac lymphatic vessel remodelling. The platform was selected for its expertise in microscopy applied to complex biological tissues and for its ability to support advanced imaging strategies.

Seeing to understand: the key contribution of light microscopy

While molecular approaches, including transcriptomics, revealed disease-associated genetic changes, microscopy was essential to visualise and validate these findings at the cellular and tissue levels. Light microscopy enabled direct observation of cardiac lymphatic structures and their organisation.

3D imaging to uncover cardiac lymphatic remodelling

Using advanced microscopy techniques, including light-sheet microscopy and deep confocal imaging, researchers accessed a three-dimensional view of the cardiac lymphatic network, not achievable with conventional histological sections. This approach demonstrated, for the first time, the presence of valves within cardiac lymphatic capillaries and loss of these structures in mice with cardiovascular disease.

Figure 4: Modification of cardiac LEC [Lymphatic endothelial cells] subpopulations post-TAC in BALB/c. (D) Examples of cardiac lymphatic valves in healthy versus post-TAC mice (Lyve1 [lymphatic marker], gray; Podocalyxin [blood capillaries marker], red; yellow arrows: lymphatic valves in capillaries, white arrowheads: valved precollectors. Scale bar, 200 µm. (E) Quantification of lymphatic capillary valves (n = 5 mice/group) in sham (white circles) and TAC (black circles), and assessment of average lymphatic intervalve distances. ##P < 0.0079 Mann–Whitney U test. Data shown as mean ± s.e.m. (Heron, C., Lemarcis, T., Laguerre, O. et al. Molecular determinants of cardiac lymphatic dysfunction in a chronic pressure-overload model. EMBO Mol Med 18, 325–355 (2026). https://doi.org/10.1038/s44321-025-00345-w)

Towards a better understanding of cardiac lymphatic dysfunction

These results highlight a link between lymphatic valve loss and impaired cardiac lymphatic drainage. By combining tailored 3D imaging and complementary transcriptomic analyses, the Rouen branch of France-BioImaging node contributed to the identification of new markers of cardiac lymphatic remodelling, opening new avenues for research into cardiovascular diseases.

Schematic view of the cardiac lymphatic dysfunction mechanism. (Heron, C., Lemarcis, T., Laguerre, O. et al. Molecular determinants of cardiac lymphatic dysfunction in a chronic pressure-overload model. EMBO Mol Med 18, 325–355 (2026). https://doi.org/10.1038/s44321-025-00345-w)

(1) Heron, C., Lemarcis, T., Laguerre, O. et al. Molecular determinants of cardiac lymphatic dysfunction in a chronic pressure-overload model. EMBO Mol Med 18, 325–355 (2026). https://doi.org/10.1038/s44321-025-00345-w

Access the scientific article here: https://link.springer.com/article/10.1038/s44321-025-00345-w