Work

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

Year: 2026

Type: article

Abstract: 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: , 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.

Source: Frontiers in Human Neuroscience

DOI: 10.3389/fnhum.2026.1854099