2024年7月29日，《免疫》杂志在线发表了天津医科大学刘强等研究人员的合作成果。该研究显示，脑缺血导致内皮细胞中的Notch1系统性活动以推动动脉粥样硬化。

研究人员发现，脑缺血引发持久的内皮激活、粘附分子VCAM1的上调以及外周内皮细胞（EC）的老化，直到中风发生后4周。这种异常的EC活性是由于持续的Notch1信号通路所致，该信号通路在中风后由于循环中的Notch1配体DLL1和Jagged1的增加而被激活，无论在小鼠还是人类中都是如此。

因此，这导致了髓系细胞粘附的增加和动脉粥样硬化进展，因为它生成了老化的、促炎的内皮。Notch1或VCAM1阻断抗体以及内皮Notch1的基因敲除减少了中风后的动脉粥样硬化进展。该研究揭示了一种系统性机制，该机制在中风后诱导外周EC的持久激活，为中风后的治疗干预或复发性血管事件的预防铺平了道路。

据介绍，中风导致持续高风险的复发性血管事件，这些事件由EC激活驱动的全身动脉粥样硬化进展所引起。然而，中风是否以及如何引发全身血管中持久的促炎和促动脉粥样硬化的内皮改变仍不清楚。

附：英文原文

Title: Brain ischemia causes systemic Notch1 activity in endothelial cells to drive atherosclerosis

Author: Mingming Liu, Danni Wang, Caiyun Qi, Ming Zou, Jiawei Song, Lili Li, Hengchang Xie, Honglei Ren, Hongying Hao, Guili Yang, Zixiao Li, Qiang Zhang, Jie Zhou, Ding Ai, Qiang Liu

Issue&Volume: 2024-07-29

Abstract: Stroke leads to persistently high risk for recurrent vascular events caused by systemicatheroprogression that is driven by endothelial cell (EC) activation. However, whetherand how stroke induces sustained pro-inflammatory and proatherogenic endothelial alterationsin systemic vessels remain poorly understood. We showed that brain ischemia inducespersistent activation, the upregulation of adhesion molecule VCAM1, and increasedsenescence in peripheral ECs until 4 weeks after stroke onset. This aberrant EC activityresulted from sustained Notch1 signaling, which was triggered by increased circulatingNotch1 ligands DLL1 and Jagged1 after stroke in mice and humans. Consequently, thisled to increased myeloid cell adhesion and atheroprogression by generating a senescent,pro-inflammatory endothelium. Notch1- or VCAM1-blocking antibodies and the geneticablation of endothelial Notch1 reduced atheroprogression after stroke. Our findingsrevealed a systemic machinery that induces the persistent activation of peripheralECs after stroke, which paves the way for therapeutic interventions or the preventionof recurrent vascular events following stroke.

DOI: 10.1016/j.immuni.2024.07.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00351-0