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oai:repisalud.isciii.es:20.500.12105/268342025-12-18T13:01:54Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc de la Cruz, Ester author Cadenas, Vanessa author Temiño, Susana author Oliver, Guillermo author Torres, Miguel author 2025-06 The contractile ability of the mammalian heart critically relies on blood coronary circulation, essential to provide oxygen and nutrients to myocardial cells. In addition, the lymphatic vasculature is essential for the myocardial immune response, extracellular fluid homeostasis and response to injury. Recent studies identified different origins of coronary lymphatic endothelial cells, however, the cues that govern coronary lymphangiogenesis remain unknown. Here we show that the coronary lymphatic vasculature develops in intimate contact with the epicardium and with epicardial-derived cells. The epicardium expresses the lymphangiogenic cytokine VEGFC and its conditional deletion in the epicardium abrogates coronary lymphatic vasculature development. Interestingly, VEGFD is also expressed in the epicardium and cooperates with VEGFC in coronary lymphangiogenesis, but it does so only in females, uncovering an unsuspected sex-specific role for this cytokine. These results identify the epicardium/subepicardium as a signaling niche required for coronary lymphangiogenesis and VEGFC/D as essential mediators of this role. EMBO Rep. 2025 Jun;26(11):2803-2818. EMBO Reports 40128409 https://hdl.handle.net/20.500.12105/26834 Coronary Vasculature Heart Development Lymphatic Vasculature Sex-specific Gene Function Vascular Biology Epicardial VEGFC/D signaling is essential for coronary lymphangiogenesis.