Data_Sheet_1_RNF213 and GUCY1A3 in Moyamoya Disease: Key Regulators of Metabolism, Inflammation, and Vascular Stability.docx

Moyamoya disease is an idiopathic chronically progressive cerebrovascular disease, which causes both ischemic and hemorrhagic stroke. Genetic studies identified RNF213/Mysterin and GUCY1A3 as disease-causing genes. They were also known to be associated with non-moyamoya intracranial large artery disease, coronary artery disease and pulmonary artery hypertension. This review focused on these two molecules and their strong linker, calcineurin/NFAT signaling and caveolin to understand the pathophysiology of moyamoya disease and related vascular diseases. They are important regulators of lipid metabolism especially lipotoxicity, NF-κB mediated inflammation, and nitric oxide-mediated vascular protection. Although intimal thickening with fibrosis and damaged vascular smooth muscle cells are the distinguishing features of moyamoya disease, origin of the fibrous tissue and the mechanism of smooth muscle cell damages remains not fully elucidated. Endothelial cells and smooth muscle cells have long been a focus of interest, but other vascular components such as immune cells and extracellular matrix also need to be investigated in future studies. Molecular research on moyamoya disease would give us a clue to understand the mechanism preserving vascular stability.

moyamoya 病是一种病因未明的慢性进展性脑血管疾病，可引发缺血性和出血性中风。遗传学研究已确定 RNF213/Mysterin 和 GUCY1A3 为致病基因。它们亦与非 moyamoya 颅内大型动脉疾病、冠状动脉疾病和肺动脉高压相关。本综述着重探讨了这些两种分子及其强关联因子——钙调神经磷酸酶/NFAT 信号传导和肌动蛋白，以揭示 moyamoya 病及相关血管疾病的病理生理机制。它们是调节脂质代谢，尤其是脂毒性、NF-κB 介导的炎症和一氧化氮介导的血管保护的重要调节因子。尽管血管内膜增厚伴纤维化和受损的血管平滑肌细胞是 moyamoya 病的显著特征，但纤维组织的起源和平滑肌细胞损伤的机制尚未完全阐明。内皮细胞和平滑肌细胞一直是研究的热点，但未来研究还需对其他血管成分，如免疫细胞和细胞外基质进行调查。对 moyamoya 病的分子研究将为我们理解维持血管稳定性的机制提供线索。