%0 Journal Article %T Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway. %A Liu HH %A Wei W %A Wu FF %A Cao L %A Yang BJ %A Fu JN %A Li JX %A Liang XY %A Dong HY %A Heng YY %A Zhang PF %J BMC Cardiovasc Disord %V 24 %N 1 %D 2024 Jul 12 %M 38992615 %F 2.174 %R 10.1186/s12872-024-03990-0 %X BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia.
METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation.
RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression.
CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.