Epicardial VEGFC/D signaling is essential for coronary lymphangiogenesis.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-03-24 DOI:10.1038/s44319-025-00431-7

Ester de la Cruz, Vanessa Cadenas, Susana Temiño, Guillermo Oliver, Miguel Torres

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Abstract

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.

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心外膜VEGFC/D信号对冠状淋巴管生成至关重要。

哺乳动物心脏的收缩能力严重依赖于血液冠状动脉循环，这是为心肌细胞提供氧气和营养所必需的。此外，淋巴血管系统对心肌免疫反应、细胞外液稳态和损伤反应至关重要。最近的研究发现了冠状淋巴管内皮细胞的不同起源，然而，支配冠状淋巴管生成的线索仍然未知。我们看到冠状淋巴管与心外膜和心外膜源性细胞密切接触。心外膜表达淋巴管生成细胞因子VEGFC，其在心外膜中的条件缺失会破坏冠状淋巴管的发育。有趣的是，VEGFD也在心外膜中表达，并在冠状淋巴管生成中与VEGFC合作，但它仅在女性中表达，揭示了该细胞因子的性别特异性作用。这些结果确定心外膜/心下膜是冠状淋巴管生成所需的信号龛，VEGFC/D是这一作用的重要介质。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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