The Notch signalling pathway is one of the main regulators of endothelial biology. In the last 20 years the critical function of Notch has been uncovered in the context of angiogenesis, participating in tip-stalk specification, arterial-venous differentiation, vessel stabilization, and maturation processes. Importantly, pharmacological compounds targeting distinct members of the Notch signalling pathway have been used in the clinics for cancer therapy. However, the underlying mechanisms that support the variety of outcomes triggered by Notch in apparently opposite contexts such as angiogenesis and vascular homeostasis remain unknown. In recent years, advances in -omics technologies together with mosaic analysis and high molecular, cellular and temporal resolution studies have allowed a better understanding of the mechanisms driven by the Notch signalling pathway in different endothelial contexts. In this review we will focus on the main findings that revisit the role of Notch signalling in vascular biology. We will also discuss potential future directions and technologies that will shed light on the puzzling role of Notch during endothelial growth and homeostasis. Addressing these open questions may allow the improvement and development of therapeutic strategies based on modulation of the Notch signalling pathway.

Notch 信号通路是内皮生物学的主要调节因子之一。在过去的 20 年中，Notch 的关键功能已在血管生成的背景下被发现，参与尖端柄规范、动静脉分化、血管稳定和成熟过程。重要的是，针对 Notch 信号通路不同成员的药理化合物已在临床中用于癌症治疗。然而，在血管生成和血管稳态等明显相反的背景下，支持 Notch 引发的各种结果的潜在机制仍然未知。近年来，随着镶嵌分析和高分子、组学技术的进步，细胞和时间分辨率研究有助于更好地理解 Notch 信号通路在不同内皮环境中驱动的机制。在这篇综述中，我们将重点关注重新审视 Notch 信号在血管生物学中的作用的主要发现。我们还将讨论潜在的未来方向和技术，这些方向和技术将阐明 Notch 在内皮生长和体内平衡中的令人费解的作用。解决这些悬而未决的问题可能有助于改进和开发基于 Notch 信号通路调节的治疗策略。我们还将讨论潜在的未来方向和技术，这些方向和技术将阐明 Notch 在内皮生长和体内平衡中的令人费解的作用。解决这些悬而未决的问题可能有助于改进和开发基于 Notch 信号通路调节的治疗策略。我们还将讨论潜在的未来方向和技术，这些方向和技术将阐明 Notch 在内皮生长和体内平衡中的令人费解的作用。解决这些悬而未决的问题可能有助于改进和开发基于 Notch 信号通路调节的治疗策略。