近日，美国哥伦比亚大学Dritan Agalliu及其小组发现，VEGF-A介导的静脉内皮细胞增殖在神经炎症期间引发新生血管形成。相关论文于2024年9月10日在线发表于国际学术期刊《自然—神经科学》。

研究人员表示，在多发性硬化症（MS）和实验性自我免疫性脑脊髓炎（EAE）的脱髓鞘急性和慢性病变中，新形成的漏血血管和血脑屏障（BBB）损伤普遍存在。然而，导致这些漏血新血管的内皮细胞亚型和信号通路尚不清楚。

通过单细胞转录组分析和体内验证，研究人员发现静脉内皮细胞表达新生血管形成基因特征，并表现出增殖增加，导致雌性成年小鼠急性和慢性EAE病变中的静脉扩张和静脉覆盖率提高。这些变化与血管内皮生长因子A（VEGF-A）信号通路的上调相关。

研究人员还确认了急性和慢性人类MS病变中新生血管形成标志物的表达增加。使用VEGF-A阻断抗体的治疗减少了雌性成年小鼠EAE中的新生血管转录组特征和血管增殖，但未能恢复BBB功能或改善EAE病理。这些数据表明，静脉内皮细胞在脱髓鞘神经炎症条件下对新生血管形成起着重要作用。

附：英文原文

Title: VEGF-A-mediated venous endothelial cell proliferation results in neoangiogenesis during neuroinflammation

Author: Shahriar, Sanjid, Biswas, Saptarshi, Zhao, Kaitao, Akcan, Uur, Tuohy, Mary Claire, Glendinning, Michael D., Kurt, Ali, Wayne, Charlotte R., Prochilo, Grace, Price, Maxwell Z., Stuhlmann, Heidi, Brekken, Rolf A., Menon, Vilas, Agalliu, Dritan

Issue&Volume: 2024-09-10

Abstract: Newly formed leaky vessels and blood–brain barrier (BBB) damage are present in demyelinating acute and chronic lesions in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the endothelial cell subtypes and signaling pathways contributing to these leaky neovessels are unclear. Here, using single-cell transcriptional profiling and in vivo validation studies, we show that venous endothelial cells express neoangiogenesis gene signatures and show increased proliferation resulting in enlarged veins and higher venous coverage in acute and chronic EAE lesions in female adult mice. These changes correlate with the upregulation of vascular endothelial growth factor A (VEGF-A) signaling. We also confirmed increased expression of neoangiogenic markers in acute and chronic human MS lesions. Treatment with a VEGF-A blocking antibody diminishes the neoangiogenic transcriptomic signatures and vascular proliferation in female adult mice with EAE, but it does not restore BBB function or ameliorate EAE pathology. Our data demonstrate that venous endothelial cells contribute to neoangiogenesis in demyelinating neuroinflammatory conditions.

DOI: 10.1038/s41593-024-01746-9

Source: https://www.nature.com/articles/s41593-024-01746-9