Journal of Shandong University (Health Sciences) ›› 2020, Vol. 58 ›› Issue (12): 8-14.doi: 10.6040/j.issn.1671-7554.0.2020.0831

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Mechanism of histone deacetylase SIRT1 inhibiting macrophages apoptosis via TLR4 signaling pathway

ZHANG Xiaolu, WANG Lili, CHEN Kaiming, LOU Xianzhi, ZHANG Man   

  1. Department of Cardiology, Central Hospital Affiliated to Shenyang Medical College, Shenyang 110024, Liaoning, China
  • Published:2020-12-08

Abstract: Objective To observe the mechanism and specific inflammatory pathways of histone deacetylase SIRT1 involved in the regulation of atherosclerosis through histone epigenetics. Methods Rats with high-fat diet and carotid artery injury and oxidized low-density lipoprotein(oxLDL)exposed macrophages under different conditions were selected as the research subjects. Apoptosis, protein expression of SIRT1, histone H3(H3), histone H3 lysine 9-site acetylation(H3K9Ac)and inflammatory factors in rats and macrophages were observed by cells function acquisition or deletion experiments. Results Compared with the control rats and macrophages, rat models with carotid artery injury and oxLDL exposed macrophages had reduced protein expression of SIRT1, increased ratio of H3K9Ac/H3, increased apoptosis, and increased protein expressions of TLR4 and IL-1β(P<0.01). After treatment of SP600125(JNK pathway antagonist), IAXO-102(TLR4 pathway antagonist), LY294002(PI3K pathway antagonist), the phenomenon of SIRT1 reduction was reversed in IAXO-102 intervention macrophages(P<0.01); after treatment of SIRT1 stimulant, apoptosis was reduced accompanied by a decreasing in the ratio of H3K9Ac/H3 and protein expressions of TLR4 and IL-1β(P<0.01). The results were reversed after treatment of SIRT1 inhibitor(P<0.01). Conclusion Histone acetylation epigenetics is involved in the regulation of apoptosis, which is closely related to the occurrence and development of atherosclerosis. Apoptosis is worsened by a decrease in histone deacetylase SIRT1 and an increase in H3 acetylation, which promotes the development of atherosclerosis, and this process must be achieved through the TLR4 signaling pathway.

Key words: Histone epigenetics, Histone deacetylase, Histone acetylation imbalance, TLR4 signaling pathway, Macrophages apoptosis

CLC Number: 

  • R541.4
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