Lipid metabolism in moyamoya disease: Emerging evidence, vascular remodeling, and therapeutic implications.

BACKGROUND

Moyamoya disease (MMD), historically termed spontaneous occlusion of the circle of Willis, is a rare steno-occlusive cerebrovascular disease. Its etiology and pathogenesis remain incompletely understood, and lipid metabolism has recently attracted attention as a potential correlate of its clinical and biological heterogeneity.

METHODS

This scoping review summarizes evidence on lipid metabolic abnormalities in MMD, including clinical associations, lipid-related markers, multi-omics findings, potential mechanisms, and therapeutic implications of lipid-modulating approaches.

RESULTS

Epidemiological studies suggest that lipid abnormalities, including hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated lipoprotein(a), are common in MMD and are associated with disease phenotype, progression, stroke risk, and postoperative outcomes. Multi-omics studies reveal lipid metabolic alterations across peripheral blood, cerebrospinal fluid (CSF), and cerebrovascular tissue, suggesting a pattern of peripheral depletion, central enrichment, and tissue remodeling. Alterations in apolipoproteins such as APOE and lipid classes including sphingolipids, cardiolipins, and lysophosphatidylcholine may be associated with endothelial and vascular smooth muscle cell dysfunction, inflammatory responses, oxidative stress, and pathological vascular remodeling. Clinical studies suggest that statin use may be associated with improved collateral formation, although the underlying mechanisms remain uncertain.

CONCLUSIONS

This review maps emerging evidence linking lipid metabolism to MMD and highlights future directions for biomarker discovery, mechanistic validation, and therapeutic exploration.