2. Academic Validation
  3. Sodium Tanshinone IIA Sulfonate alleviates vascular senescence in diabetic mice by modulating the A20-NFκB-NLRP3 inflammasome-catalase pathway

Sodium Tanshinone IIA Sulfonate alleviates vascular senescence in diabetic mice by modulating the A20-NFκB-NLRP3 inflammasome-catalase pathway

  • Sci Rep. 2024 Jul 26;14(1):17665. doi: 10.1038/s41598-024-68169-1.
Wei Wei 1 2 3,  Yan-Yan Heng 4,  Fei-Fei Wu 5,  Hao-Yu Dong 5,  Peng-Fei Zhang 4,  Jing-Xia Li 6,  Chun-Yan Liu 6,  Bing-Jie Yang 7,  Jia-Ning Fu 7,  Xin-Yue Liang 8
Affiliations

Affiliations

  • 1 Department of Pharmacology, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, 046000, Shanxi, China. jaywei@czmc.edu.cn.
  • 2 Department of Endocrinology and Institute of Endocrinology and Metabolic Disease, Heping Hospital Affiliated to Changzhi Medical College, No.110, Yanan Road South, Changzhi, 046000, Shanxi, China. jaywei@czmc.edu.cn.
  • 3 Department of Clinical Central Laboratory, Heping Hospital Affiliated to Changzhi Medical College, No.110, Yan'an South Road, Changzhi, Shanxi, China. jaywei@czmc.edu.cn.
  • 4 Department of Nephrology Heping Hospital, Affiliated to Changzhi Medical College, No.110, Yanan Road South, Changzhi, Shanxi, China.
  • 5 Department of Endocrinology and Institute of Endocrinology and Metabolic Disease, Heping Hospital Affiliated to Changzhi Medical College, No.110, Yanan Road South, Changzhi, 046000, Shanxi, China.
  • 6 Department of Anesthesia, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, Shanxi, China.
  • 7 Department of Stomatology, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, Shanxi, China.
  • 8 Department of Medical Imageology, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, Shanxi, China.
PMID: 39085294 DOI: 10.1038/s41598-024-68169-1
Abstract

Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with the deteriorative senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). For decades, Sodium Tanshinone IIA Sulfonate (STS) has been utilized as a cardiovascular medicine with acknowledged anti-inflammatory and anti-oxidative properties. Nevertheless, the impact of STS on vascular senescence remains unexplored in diabetes. Diabetic mice, primary ECs and VSMCs were transfected with the NLRP3 overexpression/knockout plasmid, the tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) overexpression/knockout plasmid, and treated with STS to detect senescence-associated markers. In diabetic mice, STS treatment maintained catalase (CAT) level and vascular relaxation, reduced hydrogen peroxide probe (ROSgreen) fluorescence, p21 immunofluorescence, Senescence β-Galactosidase Staining (SA-β-gal) staining area, and collagen deposition in aortas. Mechanistically, STS inhibited NLRP3 phosphorylation (serine 194), NLRP3 dimer formation, NLRP3 expression, and NLRP3-PYCARD (ASC) colocalization. It also suppressed the phosphorylation of IkappaB alpha (IκBα) and NFκB, preserved A20 and CAT levels, reduced ROSgreen density, and decreased the expression of p21 and SA-β-gal staining in ECs and VSMCs under HG culture. Our findings indicate that STS mitigates vascular senescence by modulating the A20-NFκB-NLRP3 inflammasome-CAT pathway in hyperglycemia conditions, offering novel insights into NLRP3 inflammasome activation and ECs and VSMCs senescence under HG culture. This study highlights the potential mechanism of STS in alleviating senescence in diabetic blood vessels, and provides essential evidence for its future clinical application.

Keywords

Catalase; Diabetic vascular disease; Endothelial cells; NLRP3 inflammasome; Senescence; Vascular smooth muscle cells.

Figures
Products