Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice
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...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-023-03485-4 |
| _version_ | 1797578233446662144 |
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| author | Yan-Yan Heng Hui-Juan Shang Xia-ze Zhang Wei Wei |
| author_facet | Yan-Yan Heng Hui-Juan Shang Xia-ze Zhang Wei Wei |
| author_sort | Yan-Yan Heng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T22:20:05Z |
| format | Article |
| id | doaj.art-2b2c6d482807434a8cab642d00267d0b |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-03-10T22:20:05Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-2b2c6d482807434a8cab642d00267d0b2023-11-19T12:18:51ZengBMCBMC Cardiovascular Disorders1471-22612023-09-0123111210.1186/s12872-023-03485-4Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic miceYan-Yan Heng0Hui-Juan Shang1Xia-ze Zhang2Wei Wei3Department of Nephrology, Heping Hospital Affiliated to Changzhi Medical CollegeDepartment of Foreign Language Teaching, Changzhi Medical CollegeThe First Clinical Acadamy of Changzhi Medical CollegeDepartment of Pharmacology, Changzhi Medical CollegeAbstract 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.https://doi.org/10.1186/s12872-023-03485-4Endothelial progenitor cellSodium tanshinone IIA sulfonateNLRP3 inflammasomeCatalaseNeointima |
| spellingShingle | Yan-Yan Heng Hui-Juan Shang Xia-ze Zhang Wei Wei Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice BMC Cardiovascular Disorders Endothelial progenitor cell Sodium tanshinone IIA sulfonate NLRP3 inflammasome Catalase Neointima |
| title | Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice |
| title_full | Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice |
| title_fullStr | Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice |
| title_full_unstemmed | Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice |
| title_short | Sodium tanshinone IIA sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice |
| title_sort | sodium tanshinone iia sulfonate ameliorates neointima by protecting endothelial progenitor cells in diabetic mice |
| topic | Endothelial progenitor cell Sodium tanshinone IIA sulfonate NLRP3 inflammasome Catalase Neointima |
| url | https://doi.org/10.1186/s12872-023-03485-4 |
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