Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.
BMC Cardiovasc Disord
; 24(1): 354, 2024 Jul 12.
Article
in En
| MEDLINE
| ID: mdl-38992615
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenanthrenes
/
Vasodilation
/
Signal Transduction
/
Matrix Metalloproteinase 2
/
Matrix Metalloproteinase 9
/
Disease Models, Animal
/
Inflammasomes
/
Syk Kinase
/
NLR Family, Pyrin Domain-Containing 3 Protein
/
Mice, Knockout, ApoE
Limits:
Animals
Language:
En
Journal:
BMC Cardiovasc Disord
Year:
2024
Document type:
Article