Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People's Republic of China.
Open Biol. 2022 Apr;12(4):220004. doi: 10.1098/rsob.220004. Epub 2022 Apr 27.
Notch signalling is an evolutionarily highly conserved signalling mechanism governing differentiation and regulating homeostasis in many tissues. In this review, we discuss recent advances in our understanding of the roles that Notch signalling plays in the vasculature. We describe how Notch signalling regulates different steps during the genesis and remodelling of blood vessels (vasculogenesis and angiogenesis), including critical roles in assigning arterial and venous identities to the emerging blood vessels and regulation of their branching. We then proceed to discuss how experimental perturbation of Notch signalling in the vasculature later in development affects vascular homeostasis. In this review, we also describe how dysregulated Notch signalling, as a consequence of direct mutations of genes in the Notch pathway or aberrant Notch signalling output, contributes to various types of vascular disease, including CADASIL, Snedden syndrome and pulmonary arterial hypertension. Finally, we point out some of the current knowledge gaps and identify remaining challenges in understanding the role of Notch in the vasculature, which need to be addressed to pave the way for Notch-based therapies to cure or ameliorate vascular disease.
Notch 信号通路是一种进化上高度保守的信号转导机制，在许多组织中调节分化和维持内稳态。在这篇综述中，我们讨论了 Notch 信号通路在脉管系统中的作用的最新认识进展。我们描述了 Notch 信号通路如何调节血管生成和重塑过程中的不同步骤（血管发生和血管生成），包括在给新生成的血管分配动脉和静脉特征以及调节其分支方面的关键作用。然后，我们继续讨论在发育后期实验性干扰 Notch 信号通路如何影响血管稳态。在这篇综述中，我们还描述了 Notch 信号通路的失调如何导致各种类型的血管疾病，包括 CADASIL、Snedden 综合征和肺动脉高压，这是 Notch 通路中基因的直接突变或异常 Notch 信号输出的结果。最后，我们指出了理解 Notch 在脉管系统中的作用的一些当前知识空白，并确定了仍需要解决的挑战，以为基于 Notch 的治疗方法治愈或改善血管疾病铺平道路。
