2. Academic Validation
  3. Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice

Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice

  • BMC Cardiovasc Disord. 2023 Sep 11;23(1):446. doi: 10.1186/s12872-023-03485-4.
Yan-Yan Heng 1,  Hui-Juan Shang 2,  Xia-Ze Zhang 3,  Wei Wei 4 5
Affiliations

Affiliations

  • 1 Department of Nephrology, Heping Hospital Affiliated to Changzhi Medical College, No.110, Yanan Road South, Changzhi, Shanxi, China.
  • 2 Department of Foreign Language Teaching, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, Shanxi, China.
  • 3 The First Clinical Acadamy of Changzhi Medical College, No.161, Jiefang East Street, Changzhi, Shanxi, China.
  • 4 Department of Pharmacology, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, 046000, Shanxi, China. [email protected].
  • 5 Department of Phase I Clinical Trial Laboratory, National Institute for Clinical Trials of Drugs, Heping Hospital Affiliated to Changzhi Medical College, No.110, South Yan'an Road, Changzhi, 046000, Shanxi, China. [email protected].
PMID: 37697234 DOI: 10.1186/s12872-023-03485-4
Abstract

Background: Endothelial progenitor cells (EPCs) transplantation is one of the effective therapies for neointima associated with endothelial injury. Diabetes impairs the function of EPCs and cumbers neointima prevention of EPC transplantation with an ambiguous mechanism. Sodium Tanshinone IIA Sulfonate (STS) is an endothelium-protective drug but whether STS protects EPCs in diabetes is still unknown.

Methods: EPCs were treated with High Glucose (HG), STS, and Nucleotide-binding Domain-(NOD) like Receptor 3 (NLRP3), Caspase-1, the Receptor of Advanced Glycation End products (AGEs) (RAGE) inhibitors, Thioredoxin-Interacting Protein (TXNIP) siRNA, and EPC proliferation, differentiation functions, and senescence were detected. The treated EPCs were transplanted into db/db mice with the wire-injured Common Carotid Artery (CCA), and the CD31 expression and neointima were detected in the CCA inner wall.

Results: We found that STS inhibited HG-induced expression of NLRP3, the production of active Caspase-1 (p20) and mature IL-1β, the expression of catalase (CAT) cleavage, γ-H2AX, and p21 in EPCs. STS restored the expression of Ki67, CD31 and von Willebrand Factor (vWF) in EPCs; AGEs were found in the HG-treated EPCs supernatant, and RAGE blocking inhibited the expression of TXNIP and the production of p20, which was mimicked by STS. STS recovered the expression of CD31 in the wire-injured CCA inner wall and the prevention of neointima in diabetic mice with EPCs transplantation.

Conclusion: STS inhibits the aggravated neointima hyperplasia by protecting the proliferation and differentiation functions of EPC and inhibiting EPC senescence in diabetic mice. The mechanism is related to the preservation of CAT activity by inhibiting the RAGE-TXNIP-NLRP3 inflammasome pathway.

Keywords

Catalase; Endothelial progenitor cell; NLRP3 inflammasome; Neointima; Sodium tanshinone IIA sulfonate.

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