Endothelial EphB4 maintains vascular integrity and transport function in adult heart
Endothelial EphB4 maintains vascular integrity and transport function in adult heart
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DOI：
10.7554/elife.45863
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发表时间：
2019-11-29
期刊：
影响因子：
7.7
通讯作者：
Adams, Ralf H.
中科院分区：
文献类型：
--
作者：
Luxan, Guillermo;Stewen, Jonas;Adams, Ralf H.
心脏和其他器官的稳态依赖于适当的营养供应和局部脉管系统的功能专业化。在这里，我们使用小鼠遗传学、成像和细胞生物学方法来研究内皮 EphB4 及其配体 ephrin-B2 如何控制成人心脏的稳态，它们是发育过程中血管形态发生和动静脉分化的已知调节因子。我们发现，成年小鼠中 Ephb4 的诱导型和内皮细胞特异性失活与存活相容，但会导致心肌毛细血管破裂、心肌细胞肥大和病理性心脏重塑。相比之下，EphB4 并不是骨骼肌毛细血管完整性和稳态所必需的。我们对突变小鼠和培养的内皮细胞的分析表明，EphB4 控制着小凹的功能、机械应力下的细胞间粘附和脂质运输。我们认为 EphB4 维持成人心脏血管系统的关键功能特性，从而预防扩张型心肌病样缺陷。
The homeostasis of heart and other organs relies on the appropriate provision of nutrients and functional specialization of the local vasculature. Here, we have used mouse genetics, imaging and cell biology approaches to investigate how homeostasis in the adult heart is controlled by endothelial EphB4 and its ligand ephrin-B2, which are known regulators of vascular morphogenesis and arteriovenous differentiation during development. We show that inducible and endothelial cell-specific inactivation of Ephb4 in adult mice is compatible with survival, but leads to rupturing of cardiac capillaries, cardiomyocyte hypertrophy, and pathological cardiac remodeling. In contrast, EphB4 is not required for integrity and homeostasis of capillaries in skeletal muscle. Our analysis of mutant mice and cultured endothelial cells shows that EphB4 controls the function of caveolae, cell-cell adhesion under mechanical stress and lipid transport. We propose that EphB4 maintains critical functional properties of the adult cardiac vasculature and thereby prevents dilated cardiomyopathy-like defects.