Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (25): 5351-5361.doi: 10.12307/2025.508

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Histone deacetylase 1 gene inhibits pyroptosis of human umbilical vein endothelial cells and alleviates atherosclerosis and inflammatory response

Zhang Guoan1, Shi Jian1, Song Baoguo1, Huang Xiaoyan2   

  1. 1Department of Cardiovascular Surgery, 2Shaanxi Provincial Key Laboratory of Infection and lmmune Diseases, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
  • Received:2024-01-20 Accepted:2024-04-19 Online:2025-09-08 Published:2024-12-24
  • Contact: Huang Xiaoyan, Master, Associate chief physician, Shaanxi Provincial Key Laboratory of Infection and lmmune Diseases, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
  • About author:Zhang Guoan, Master, Attending physician, Department of Cardiovascular Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
  • Supported by:
    Shaanxi Province Key Research & Development Plan Project, No. 2023-YBSF-672 (to SJ)

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Abstract: BACKGROUND: Pyroptosis, as a unique form of inflammatory cell death, plays an important role in the instability of atherosclerotic lesions.
OBJECTIVE: To explore the action mechanism of recombinant B-cell lymphoma 2-related protein A1 (BCL2A1) in atherosclerosis. 
METHODS: (1) Human umbilical vein endothelial cells were treated with 200 μg/mL oxidized low-density lipoprotein for 24 hours to induce endothelial injury. Subsequently, 50 nmol/L BCL2A1 interfering plasmid (BCL2A1 short hairpin RNA, sh-BCL2A1) and 1.5 μg/mL histone deacetylase 1 gene (HDAC1) overexpression vector (pcDNA-HDAC1) was transfected into human umbilical vein endothelial cells, or both pcDNA-HDAC1 and BCL2A1 overexpression vector (pcDNA-BCL2A1) were transfected simultaneously. After 48 hours of cell culture, the expression levels of BCL2A1 and HDAC1, cell viability, cell pyroptosis level, and BCL2A1 acetylation level were detected. (2) The atherosclerosis mouse model was constructed by high-fat feeding APOE-/- mouse for in vivo verification. 500 μL of BCL2A1 and HDAC1 lentiviral overexpression vectors were injected into mice via tail vein, respectively or simultaneously. The expression levels of BCL2A1 and HDAC1 and the damage of arterial tissue in mice were detected. 
RESULTS AND CONCLUSION: The expression of BCL2A1 was upregulated in human umbilical vein endothelial cells induced by oxidized low-density lipoprotein. Interference of BCL2A1 improved cell viability and inhibited pyroptosis and inflammatory response. In addition, HDAC1 was down-regulated in oxidized low-density lipoprotein-induced human umbilical vein endothelial cells. Cell viability was elevated and pyroptosis and inflammatory response were inhibited by promoting BCL2A1 deacetylation. In vivo experiments showed that BCL2A1 was highly expressed in arterial tissues of mice fed with high-fat diet, while HDAC1 was lowly expressed. Additionally, HDAC1 alleviated high-fat diet-induced arterial tissue lesions in ApoE-/- mice by promoting the deacetylation of BCL2A1. It is concluded that HDAC1 may inhibit pyroptosis of human umbilical vein endothelial cells by deacetylating BCL2A1 to reduce atherosclerosis and inflammatory response.

Key words: atherosclerosis, BCL2A1, HDAC1, acetylation, cell pyroptosis

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