Histidine triad nucleotide-binding protein 2 inhibits progression of athero-sclerosis by regulating macrophage pyroptosis
10.3969/j.issn.1000-4718.2024.06.003
- VernacularTitle:组氨酸三联体核苷酸结合蛋白2通过调控巨噬细胞焦亡抑制动脉粥样硬化
- Author:
Hui GAO
1
;
Xinyi ZHANG
;
Yuli GUO
;
Ruiting FENG
;
Rui WANG
;
Yu LIU
;
Min GUO
Author Information
1. 山西医科大学第一临床医学院,山西 太原 030000
- Keywords:
histidine triad nucleotide-binding protein 2;
macrophages;
pyroptosis;
atherosclerosis
- From:
Chinese Journal of Pathophysiology
2024;40(6):980-988
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To explore the impact of histidine triad nucleotide-binding protein 2(HINT2)on atheroscle-rosis(AS),and to elucidate its underlying mechanisms.METHODS:Peripheral blood mononuclear cells(PBMCs)were isolated from patients with chest pain and induced to differentiate into macrophages for assessing HINT2 expression.In vitro,RAW264.7 mouse macrophages were cultured to evaluate inflammatory cytokine levels and cell death in superna-tants.An apolipoprotein E gene knockout(apoE-/-)mouse model of AS was developed to analyze plaque formation,lipid metabolism and macrophage foaminess in the aortic root.Pyroptosis-related protein expression in cultured RAW264.7 cells and the aorta of apoE-/-mice was determined by RT-qPCR and Western blot.RESULTS:Significantly reduced HINT2 expression was observed in PBMCs from patients with acute coronary syndrome,which was negatively correlated with pro-inflammatory and positively correlated with anti-inflammatory serum factors,suggesting HINT2's potential role in mitigating AS-related inflammation.In vitro experiments demonstrated that HINT2 overexpression inhibited lipid accumu-lation and foam cell formation in macrophages induced by oxidized low-density lipoprotein(ox-LDL).It also reduced se-cretion of inflammatory cytokines,including interleukin-6(IL-6),IL-1β,IL-18 and tumor necrosis factor-α,and de-creased cell death and pyroptosis-related protein expression.In vivo experiments in apoE-/-mice confirmed that HINT2 overexpression lessened plaque burden in the aortic root,reduced macrophage foaminess,and inhibited the expression of pyroptosis-related proteins such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,gasdermin D(GSDMD),IL-1β and IL-18.CONCLUSION:HINT2 potentially inhibits ox-LDL-induced macrophage pyroptosis,attenuates inflammatory responses in AS,and may slow the progression of this disease.
