Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (32): 6836-6842.doi: 10.12307/2025.941

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Spermidine/spermine N1-acetyltransferase 1 participates in vascular smooth muscle cell calcification

Wang Kairu1, 2, 3, 4, Fu Shizhe1, 2, 3, 4, Li Jiahui1, 3, 4, Yan Ru1, 3, 4, 5, Ma Yuru1, 3, 4, 5, Shi Bo1, 2, 3, 4, Ye Congyan1, 2, 3, 4, Yan Rui1, 2, 3, 4, Cong Guangzhi1, 3, 4, 5, Jia Shaobin1, 3, 4, 5   

  1. 1Institute of Medical Research, 5Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 2First Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 3Key Laboratory of Metabolic Cardiovascular Disease Research, National Health Commission, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 4Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Received:2024-10-14 Accepted:2024-12-10 Online:2025-11-18 Published:2025-04-25
  • Contact: Jia Shaobin, Doctoral supervisor, Professor, Chief physician, Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Institute of Medical Research, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Metabolic Cardiovascular Disease Research, National Health Commission, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China Co-corresponding author: Cong Guangzhi, PhD, Master’s supervisor, Associate chief physician, Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Institute of Medical Research, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Metabolic Cardiovascular Disease Research, National Health Commission, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • About author:Wang Kairu, Master candidate, Institute of Medical Research, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; First Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Metabolic Cardiovascular Disease Research, National Health Commission, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China, No. 82260086 (to JSB); Ningxia Heart Valve Disease Standardized Diagnosis and Treatment Technology Application Demonstration, No. 2022FRD05046 (to JSB) 

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Abstract: BACKGROUND: Polyamines play a crucial role in tissue calcification. Spermidine/spermine N1-acetyltransferase 1(SAT1), as a key rate-limiting enzyme regulating intracellular polyamine metabolism, has been associated with various pathological processes. However, its role in vascular calcification remains unclear.
OBJECTIVE: To investigate the role of SAT1 in rat vascular smooth muscle cell calcification. 
METHODS: (1) Bioinformatics analysis: Differential expression of SAT1 in human carotid atherosclerotic plaques and their surrounding healthy carotid artery tissues were using GEO datasets. PanglaoDB database was used to analyze SAT1 expression abundance and localization across different cell types through single-cell sequencing. (2) Rat vascular smooth muscle cells were divided into three groups: a control group cultured in DMEM medium, a calcification group induced by DMEM medium containing 10 mmol/L β-glycerophosphate sodium and 3 mmol/L calcium chloride, and the 50, 100 μmol/L diacetylaminotriazamidine groups treated with the SAT1 inhibitor, diacetylaminotriazamidine, in addition to the calcification medium. After 7-10 days of culture, alizarin red S staining was performed, and cellular calcium content and alkaline phosphatase activity were assessed. Western blot was used to detect the protein expression of Runt-related transcription factor 2, bone morphogenetic protein 2, alpha-smooth muscle actin, and SAT1. Immunofluorescence staining was conducted to examine the expression of Runt-related transcription factor 2 and SAT1.   
RESULTS AND CONCLUSION: (1) Bioinformatics analysis revealed significantly upregulated expression of SAT1 and Runt-related transcription factor 2 (P < 0.05) in carotid atherosclerotic plaques compared with healthy carotid tissues (P < 0.05). Single-cell sequencing database analysis confirmed SAT1 expression in vascular smooth muscle cells. (2) Compared with the control group, the calcification group showed significantly increased Runt-related transcription factor 2, bone morphogenetic protein 2, SAT1, calcium content, and alkaline phosphatase activity, while alpha-smooth muscle actin expression was significantly decreased (all P < 0.05). Compared with the calcification group, the 50 and 100 μmol/L diacetylaminotriazamidine groups showed significantly decreased Runt-related transcription factor 2, bone morphogenetic protein 2, calcium content, and alkaline phosphatase activity, while alpha-smooth muscle actin expression was significantly increased (all P < 0.05). (3) Immunofluorescence experiments demonstrated that compared with the calcification group, the expression intensity of Runt-related transcription factor 2 was significantly reduced in the 50 and 100 μmol/L diacetylaminotriazamidine groups. Overall, SAT1 may promote vascular smooth muscle cell calcification by upregulating Runt-related transcription factor 2 expression.  

Key words: rat vascular smooth muscle cells, spermidine/spermine N1-acetyltransferase 1 (SAT1), Runt-related transcription factor 2, vascular calcification, bioinformatics, smooth muscle actin

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