中国病理生理杂志2024，Vol.40Issue(6)：980-988,9.DOI:10.3969/j.issn.1000-4718.2024.06.003
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
Histidine triad nucleotide-binding protein 2 inhibits progression of athero-sclerosis by regulating macrophage pyroptosis
摘要
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.关键词
组氨酸三联体核苷酸结合蛋白2/巨噬细胞/细胞焦亡/动脉粥样硬化Key words
histidine triad nucleotide-binding protein 2/macrophages/pyroptosis/atherosclerosis分类
医药卫生引用本文复制引用
高慧,张昕怡,郭玉莉,冯睿婷,王睿,刘宇,郭敏..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[J].中国病理生理杂志,2024,40(6):980-988,9.基金项目
国家自然科学基金资助项目(No.82000426) （No.82000426）
