Chili-derived exosome-like nanovesicle antagonize the transformation of macrophages into foam cells through ERK1/2 pathway
10.20039/j.cnki.1007-3949.2024.06.007
- VernacularTitle:辣椒来源外泌体样纳米囊泡通过ERK1/2通路拮抗巨噬细胞向泡沫细胞转化
- Author:
Wenlin WANG
1
,
2
;
Ye LUO
;
Xiao KE
Author Information
1. 南华大学中国医学科学院阜外医院深圳医院协作培养基地,广东省深圳市 518057
2. 中国医学科学院阜外医院深圳医院心内科,广东省深圳市 518057
- Keywords:
atherosclerosis;
chili-derived exosome-like nanovesicle;
foam cell;
MAPK;
macrophage
- From:
Chinese Journal of Arteriosclerosis
2024;32(6):503-513
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate how chili-derived exosome-like nanovesicle(CDELN)inhibited ox-LDL uptake and reduced ox-LDL-induced intracellular cholesterol accumulation.Methods CDELN were isolated and purified using tissue crushing,differential centrifugation,ultracentrifugation and sucrose density gradient centrifugation.Ox-LDL was used to stimulate THP-1-derived macrophages for 24 hours to establish a foam cell model in vitro,and the effect of CDELN on macrophage foam and its mechanism were further studied.Confocal laser microscopy was used to detect the uptake of CDELN and DiL-acetylated low density lipoprotein(DiL-ac-LDL)by THP-1 macrophages.Oil red O staining was used to detect intracellular cholesterol content and the positive area of oil red 0 staining in cells was analyzed to evalu-ate the effect of intracellular lipid accumulation.RT-qPCR and Western blot were used to detect mRNA and protein levels of scavenger receptor A(SRA)and cluster of differentiation 36(CD36),lectin-like oxidized low density lipoprotein recep-tor-1(LOX-1),ATP-binding cassette transporter A1/G1(ABCA1/G1).The expression of mitogen-activated protein ki-nase(MAPK)pathway proteins including p-ERK,p-p38 MAPK and p-c-Jun,were also analyzed.Results CDELN were exosome-like nanovesicles with uniform size and double membrane,rich in protein and nucleic acids,which can be taken up by macrophages.The results of DiL-ac-LDL uptake showed that CDELN could inhibit cholesterol uptake of mac-rophages.Oil red 0 staining showed that CDELN could reduce ox-LDL-induced intracellular cholesterol accumulation.RT-qPCR and Western blot showed that CDELN could significantly reduce mRNA levels of matrix metalloprotein-9(MMP-9),SRA,CD36 and LOX-1 and protein levels of p-ERK,SRA,CD36 and LOX-1 in ox-LDL-induced THP-1-derived macro-phages.Treatment with the p-ERK agonist Yoda1 diminished the protective effect of CDELN.Conclusion CDELN can significantly inhibit macrophage foam cell formation,and this effect may be associated with the inhibition of phosphoryl-ation levels of ERK1/2 in the MAPK pathway.
