2. Academic Validation
  3. Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway

Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway

  • BMC Cardiovasc Disord. 2024 Jul 12;24(1):354. doi: 10.1186/s12872-024-03990-0.
Hai-Hua Liu 1,  Wei Wei 2 3 4,  Fei-Fei Wu 1,  Lu Cao 1,  Bing-Jie Yang 5,  Jia-Ning Fu 5,  Jing-Xia Li 6,  Xin-Yue Liang 7,  Hao-Yu Dong 1,  Yan-Yan Heng 8,  Peng-Fei Zhang 8
Affiliations

Affiliations

  • 1 Department of Endocrinology, Heping Hospital Affiliated to Changzhi Medical College, No.110, Yan'an South Road, Changzhi, 046000, Shanxi, China.
  • 2 Department of Endocrinology, Heping Hospital Affiliated to Changzhi Medical College, No.110, Yan'an South Road, Changzhi, 046000, Shanxi, China. jaywei@czmc.edu.cn.
  • 3 Department of Pharmacology, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, 046000, Shanxi, China. jaywei@czmc.edu.cn.
  • 4 Department of Clinical Center Laboratory, Heping Hospital Affiliated to Changzhi Medical College, No.110, Yan'an South Road, Changzhi, 046000, Shanxi, China. jaywei@czmc.edu.cn.
  • 5 Department of Stomatology, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, 046000, Shanxi, China.
  • 6 Department of Anesthesia, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, 046000, Shanxi, China.
  • 7 Department of Medical Imageology, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, 046000, Shanxi, China.
  • 8 Department of Nephrology Heping Hospital, Changzhi Medical College, No.110, Yanan Road South, Changzhi, 046000, Shanxi, China.
PMID: 38992615 DOI: 10.1186/s12872-024-03990-0
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.

Keywords

Hyperlipidemia; MMP2/9; NLRP3 inflammasome; Sodium tanshinone IIA sulfonate; Vascular relaxation.

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