Sulfur Dioxide Alleviates Aortic Dissection Through Inhibiting Vascular Smooth Muscle Cell Phenotype Switch,...

Area of Science:

• Biochemistry
• Molecular Biology
• Cardiovascular Research

Background:

• Abnormal vascular smooth muscle cell (VSMC) migration and proliferation are key in thoracic aortic dissection (TAD).
• Endogenous sulfur dioxide (SO2), produced by aspartate aminotransferase (AAT1), inhibits VSMC migration and proliferation.
• The specific role of SO2 in TAD pathogenesis is not well understood.

Purpose of the Study:

• To investigate the role of endogenous SO2 in TAD.
• To elucidate the regulatory network involving SO2, microRNAs (miRNAs), and VSMC function in TAD.
• To identify potential therapeutic targets for TAD.

Main Methods:

• Analysis of aortic samples from TAD patients to measure SO2 production.
• Mouse models of vascular injury to assess SO2 supplementation effects.
• MicroRNA sequencing to identify dysregulated miRNAs after AAT1 knockdown.
• In vitro studies to examine the effects of manipulating the SO2 pathway, miR-184-3p, and Cyp26b1 on VSMC function.

Main Results:

• Reduced endogenous SO2 production was observed in TAD patient aortic samples.
• SO2 supplementation ameliorated vascular injury in a mouse model.
• AAT1 knockdown led to increased miR-184-3p expression, targeting Cyp26b1.
• Decreased SO2 pathway impaired VSMC function via reduced Cyp26b1; restoring Cyp26b1 with miR-184-3p inhibitors improved function.

Conclusions:

• Endogenous SO2 plays a protective role in TAD by inhibiting VSMC migration and proliferation.
• The miR-184-3p/Cyp26b1 axis is a crucial component of the endogenous SO2 regulatory network in VSMCs.
• Targeting the SO2 pathway or the miR-184-3p/Cyp26b1 axis presents a potential therapeutic strategy for TAD.