BCAT1 affects atherosclerosis in the elderly by regulating macrophage foam cell formation
10.16753/j.cnki.1008-2344.2025.05.011
- VernacularTitle:BCAT1通过调节巨噬细胞泡沫化影响老年动脉粥样硬化
- Author:
Lili TAN
1
;
Jie LU
Author Information
1. 沈阳医学院附属中心医院心血管内科,辽宁 沈阳 110024
- Publication Type:Journal Article
- Keywords:
branched-chain amino acid transaminase 1(BCAT1);
atherosclerosis in the elderly;
macrophage foam cell formation
- From:
Journal of Shenyang Medical College
2025;27(5):507-513
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the expression changes of branched-chain amino acid transaminase 1(BCAT1)in the process of atherosclerosis(AS)in the elderly and its regulatory effect on macrophage foam cell formation,thereby revealing the potential pathogenesis of AS in the elderly.Methods:AS mouse models were established by feeding a high-fat diet in vivo.The expression and co-localization of BCAT1 and CD68 in aortic tissues of mice were detected by immunofluorescence double staining.Hematoxylin-eosin staining and Oil Red O staining were used to observe the pathological damage and lipid deposition in the aortic root tissues of mice.The expression of TNF-α,IL-6 and IL-1β in aortic tissues was determined by qPCR.In vitro,RAW264.7 mouse macrophage cells were stimulated with ox-LDL.The expression of BCAT1 in cells was detected by Western blot.Oil Red O staining was used to detect lipid accumulation and foam cell formation in cells.The contents of TNF-α,IL-6 and IL-1β in the cell supernatant were detected by ELISA.Results:Compared with the control group,the expression of BCAT1 in aortic tissues of AS mice was upregulated,and this protein was mainly localized in infiltrating macrophages(CD68+cells).The lipid content in atherosclerotic plaques of AS mice was significantly increased,the arterial wall was significantly thickened,and the infiltration of inflammatory cells was aggravated.Overexpression of BCAT1 further exacerbated AS lesions in aortic tissues of mice.The mRNA expression levels of TNF-α,IL-6 and IL-1β in the aorta of AS mice were significantly higher than those in the control group,and overexpression of BCAT1 further upregulated the mRNA expression levels of pro-inflammatory cytokines.In vitro,ox-LDL treatment significantly upregulated the protein expression of BCAT1 in RAW264.7 cells,increased intracellular lipid accumulation and foam cell formation,and promoted the release of pro-inflammatory cytokines.Overexpression of BCAT1 promoted lipid accumulation,foam cell formation and the release of pro-inflammatory cytokines in cells,while knockdown of BCAT1 showed the opposite trend.Conclusion:BCAT1 is involved in the development process of AS and increases the secretion of pro-inflammatory cytokines,promotes macrophage foam cell formation and inflammatory response,suggesting that BCAT1 plays a key role in the development of AS in the elderly.