昼夜节律时钟是一种内部生物钟，能够将生理和基因表达与24小时太阳日协调。哺乳动物的昼夜节律时钟扰动已与血管功能紊乱有关，并且已暗示昼夜节律时钟在血管生成中的功能。然而，昼夜节律时钟在内皮细胞（EC）中的功能作用以及对血管生成调节的影响还有待于进一步探索。在这里，我们使用体内和体外方法证明EC拥有内源性分子时钟，并显示核心时钟基因强劲的昼夜节律振荡。通过在体内损害BMAL1转录激活因子在EC特定功能，我们发现小鼠新生血管组织中的血管生成缺陷以及成人肿瘤血管生成设置中的血管生成缺陷。然后，我们调查了培养的EC中昼夜节律时钟机制的功能，并显示出BMAL和CLOCK敲除会影响EC的细胞周期进展。通过使用RNA-和ChIP-seq基因组宽方法，我们确定BMAL1结合CCNA1和CDK1基因的启动子，并在EC中控制其表达。我们的研究结果表明，EC表现出强有力的昼夜节律时钟，BMAL1在发育和病理情况下调节EC生理。BMAL1的遗传改变可以影响体内和体外情况下的血管生成。这些发现支持探索在血管疾病中操作昼夜节律时钟的必要性。进一步研究BMAL1及其靶基因在肿瘤内皮中的行为可以发现干预肿瘤上皮昼夜节律的新治疗方法。© 作者（们）2023年。由牛津大学出版社代表欧洲心脏病学会出版。保留所有权利。有关权限，请发送电子邮件至：journals.permissions@oup.com。

The circadian clock is an internal biological timer that coordinates physiology and gene expression with the 24-hour solar day. Circadian clock perturbations have been associated to vascular dysfunctions in mammals and a function of the circadian clock in angiogenesis has been suggested. However, the functional role of the circadian clock in endothelial cells (EC) and in the regulation of angiogenesis is widely unexplored.Here, we used both in vivo and in vitro approaches to demonstrate that EC possess an endogenous molecular clock and show robust circadian oscillations of core clock genes. By impairing the EC-specific function of the circadian clock transcriptional activator BMAL1 in vivo, we detect angiogenesis defects in mouse neonatal vascular tissues, as well as in adult tumor angiogenic settings. We then investigate the function of circadian clock machinery in cultured EC and show evidence that BMAL and CLOCK knock-down impair EC cell cycle progression. By using an RNA- and ChIP-seq genome-wide approaches we identified that BMAL1 binds the promoters of CCNA1 and CDK1 genes and controls their expression in EC.Our findings show that EC display a robust circadian clock and that BMAL1 regulates EC physiology in both developmental and pathological contexts. Genetic alteration of BMAL1 can affect angiogenesis in in vivo and in vitro settings.These findings support the need to explore the manipulation of the circadian clock in vascular diseases. Further investigation of the behavior of BMAL1 and its target genes in the tumor endothelium can aim to discover novel therapeutic interventions to interfere with the endothelial circadian clock in the tumor context.© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.