STK39 is associated with endothelial dysfunction and inflammatory activation under hypoxic conditions in moyamoya disease

Objective Moyamoya disease (MMD) is a cerebrovascular disease whose mechanism relatively unknown and can cause vascular occlusion and hyperplasia. This study aimed to explore molecular heterogeneity associated with the expression of acetylation-related genes in MMD and to identify candidate genes potentially involved in vascular endothelial dysfunction. Methods Public MMD transcriptomic datasets were analyzed using a predefined acetylation-regulatory gene set to identify expression clusters and prioritize cluster-associated candidate genes. Functional enrichment, immune-infiltration, and predicted miRNA–mRNA network analyses were performed to characterize candidate-associated molecular features. Serum STK39 and MTMR12 concentrations were assessed by ELISA in a preliminary study of three patients with MMD and three healthy controls. STK39 was further investigated in human brain microvascular endothelial cells (HBMECs) using siRNA-mediated knockdown under normoxic and hypoxic conditions, with Trichostatin A (TSA) treatment included as an exploratory pharmacological intervention. Results Consensus clustering was used to classify MMD into two subtypes, and five key subtype-related genes were identified: STK39, NEO1, PKNOX1, GOLT1B, and MTMR12. In the validation cohort, serum STK39 and MTMR12 levels were significantly decreased in patients with MMD. In vitro , STK39 knockdown promoted HBMEC migration, inhibited proliferation, and increased the expression of HIF-1α, p-STAT3, cleaved Caspase-3, IL-6, CCL2, and VCAM-1 under hypoxic conditions, whereas TSA treatment partially reversed these changes. Conclusion Acetylation-related genes are closely associated with the molecular heterogeneity of MMD. Among them, STK39 appears to participate in hypoxia-related endothelial dysfunction and inflammatory activation. These findings provide new insight into the role of acetylation-related pathways in MMD pathogenesis and suggest potential targets for future mechanistic studies.