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.