GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease

 Huiqin Li1 · Xiang Cao1,2,4,5,6,7 · Xinya Gu3 · Mengqi Dong4 · Lili Huang1 · Chenglu Mao1 · Shengnan Xia1 · Haiyan Yang1 · Xinyu Bao1 · Yongbo Yang1 · Yun Xu1,2,3,4,5,6,7
1 Department of Neurology and Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China
2 Department of Neurology and Neurosurgery, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China
3 Department of Neurology and Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing 210008, China
4 Department of Neurology and Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
5 Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing 210008, China
6 Jiangsu Provincial Key Discipline of Neurology, Nanjing 210008, China
7 Nanjing Neurology Medical Center, Nanjing 210008, China

Abstract
Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels. Immune inflammation is associated with the occurrence and development of MMD. However, the mechanisms underlying the formation of the abnormal vascular network remain unclear. Twenty-eight patients with MMD, 26 ischemic stroke patients, and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were higher in MMD patients than in healthy controls (P <0.01), and GM-CSF was mainly from Th1 and Th17 cells in MMD. We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis, inflammation, and chemotaxis. In summary, our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

Keywords
Moyamoya disease; Vascular endothelial cells; GM-CSF; VEGF