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GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease
Huiqin Li1, Xiang Cao1,2,3,4,5,6, Xinya Gu7
1Department of Neurology and Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 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.
Insights
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is elevated in Moyamoya disease (MMD) patients, originating from Th1 and Th17 cells. This factor drives monocyte cytokine secretion, contributing to abnormal vascular network formation in MMD.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- Moyamoya disease (MMD) is a chronic cerebrovascular condition characterized by abnormal vessel development.
- Immune inflammation plays a role in MMD pathogenesis, but the mechanisms of abnormal vascular network formation are not fully understood.
Purpose of the Study:
- To investigate the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in Moyamoya disease.
- To elucidate the cellular sources and downstream effects of GM-CSF in MMD.
Main Methods:
- Comparative analysis of GM-CSF levels in MMD patients, ischemic stroke patients, and healthy controls.
- Identification of GM-CSF-producing immune cells (Th1 and Th17 cells) in MMD patients.
- Assessment of GM-CSF's impact on monocyte-derived cytokine profiles related to angiogenesis, inflammation, and chemotaxis.
Main Results:
- GM-CSF levels were significantly higher in MMD patients compared to healthy controls (P <0.01).
- GM-CSF primarily originated from Th1 and Th17 cells within the MMD patient group.
- Elevated GM-CSF stimulated monocytes to secrete cytokines involved in angiogenesis, inflammation, and cell recruitment.
Conclusions:
- GM-CSF is significantly implicated in the pathogenesis of Moyamoya disease.
- GM-CSF acts as a key mediator in the formation of abnormal vascular networks characteristic of MMD.
