PhD Scientific Days 2026

Molecular Medicine 3.

The Role of Tenascin-C and Cardiac Lymphatics in Left Ventricular Hypertrophy: Insights from a Mouse Model

Name of the presenter

Molnár, Kornél

Institute/workplace of the presenter

Department of Physiology

Authors

Kornél Molnár¹, Zsombor Ocskay¹, Lukas Weber², Chenming Hu², Nathalie Schiessler², Matthias Ernst², Bruno Podesser², Attila Kiss², Zoltán Jakus¹
1: Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2: Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, Austria

Text of the abstract

Left ventricular hypertrophy (LVH) induced by chronic pressure overload, along with the associated risk of heart failure, can be partially mitigated by pharmacological therapies; however, its reversal remains challenging. Region-specific alterations in cardiac lymphatics may contribute to adverse tissue remodeling in LVH, yet their spatial and temporal regulation remains poorly defined, particularly given emerging evidence that the extracellular matrix protein Tenascin-C (TNC) regulates lymphangiogenesis.
We aimed to investigate the spatiotemporal alterations of cardiac lymphatics and to examine the role of TNC in lymphangiogenesis and in tissue remodeling during pressure overload-induced LVH.
LVH was induced in adult male wild-type and TNC knockout (KO) mice by transverse aortic constriction (TAC); sham-operated wild-type mice served as controls. Animals were sacrificed 1 or 6 weeks after surgery. Cardiac morphology was assessed by Masson’s trichrome and hematoxylin–eosin staining, while lymphatics and TNC expression in arterial perivascular regions were evaluated by fluorescent immunohistochemistry. In vitro, human lymphatic endothelial cells (LECs) were treated with human recombinant TNC, followed by viability assays.
Histological analyses revealed marked, region-specific alterations in lymphatic distribution in the heart under chronic pressure overload compared to sham-operated controls. Spatial and temporal analyses demonstrated that lymphatic remodeling is highly region-dependent. In wild-type mice, pressure overload reduced lymphatic density in arterial perivascular regions, concomitant with increased TNC expression. In contrast, TNC deficiency was associated with an increased number and perimeter of lymphatic vessels, along with the mitigation of adverse cardiac remodeling. In vitro findings further indicated that TNC dose-dependently negatively affects LEC viability and promotes pro-inflammatory and fibrotic endothelial–mesenchymal transition.
These findings suggest that pressure overload reduces periarterial cardiac lymphatics, potentially mediated by TNC. TNC may act as a regulator of lymphangiogenesis and cardiac remodeling, representing a potential therapeutic target. Further studies are needed to clarify the underlying mechanisms.
K139165, TKP2021-EGA-29, TKP2021-EGA-24, 2023-1.2.4-TÉT-2023-00053, 2025-1.2.1-HU-RIZONT-2025-00028