Sulfur Dioxide Alleviates Aortic Dissection Through Inhibiting Vascular Smooth Muscle Cell Phenotype Switch, Migration, and Proliferation via miR-184-3p/Cyp26b1 Axis

Aims: Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are considered early events in the onset of thoracic aortic dissection (TAD). Endogenous sulfur dioxide (SO2), primarily produced by aspartate aminotransferase (AAT1) in mammals, has been reported to inhibit the migration and proliferation of VSMCs. However, the role of SO2 in the development of TAD remains unclear. Results: Endogenous SO2 production was decreased in aortic samples from patients with TAD. Supplementation with SO2 ameliorated β-aminopropionitrile-induced vascular injury in mice. Increasing the expression of SO2 pathway might reverse the abnormal migration, proliferation, and phenotypic switching in VSMCs. MicroRNA sequencing revealed miR-184-3p as the miRNA with the most significant increased expression level after AAT1 knockdown, and Cyp26b1 was predicted to be its potential target. A decrease in the SO2 pathway resulted in reduced Cyp26b1 expression, impairing VSMCs function, while restoring Cyp26b1 expression with miR-184-3p inhibitors could improve the VSMCs function. Innovation: This research extends the application of endogenous SO2 to the aortic diseases and elucidates the role of miRNA in endogenous SO2 regulatory network, highlighting its potential as a target for clinical practice. Conclusion: Endogenous SO2 inhibits the migration and proliferation of VSMCs in TAD progression via the miR-184-3p/Cyp26b1 axis. Antioxid. Redox Signal. 00, 000-000.