Exosomes derived from baicalin-pretreated mesenchymal stem cells mitigate atherosclerosis by regulating the SIRT1/NF-κB signaling pathway

被引:0
作者
Yang, Xiaochun [1 ]
Wu, Wei [1 ]
Huang, Weitian [2 ]
Fang, Junfeng [3 ]
Chen, Yunli [2 ]
Chen, Xiaoyan [2 ]
Lin, Xiaolan [2 ]
He, Yanbin [2 ]
机构
[1] Guangzhou Univ Chinese Med, Clin Coll Med 1, Guangzhou 510405, Guangdong, Peoples R China
[2] Guangdong Work Injury Rehabil Hosp, Dept Rehabil, Guangzhou 510000, Guangdong, Peoples R China
[3] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Emergency, Guangzhou 510000, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
exosomes; mesenchymal stem cells; baicalin; atherosclerosis; inflammation; NF-KAPPA-B; MACROPHAGE POLARIZATION; INFLAMMATION; SIRT1; DELIVERY; THERAPY; INJURY;
D O I
10.3892/mmr.2025.13491
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Atherosclerosis (AS) is a disease with high global incidence and mortality rates. Currently, the treatment of AS in clinical practice carries a high risk of adverse effects and toxic side effects. The pretreatment of mesenchymal stem cells (MSCs) with drugs may enhance the bioactivity of MSC-derived exosomes (MSC-exos), which could be a promising candidate for inhibiting the progression of AS. The aim of the present study was to investigate the ability of exos derived from baicalin-preconditioned MSCs (Ba-exos) to exhibit an inhibitory effect on AS progression and to explore the potential molecular mechanisms. Exos were isolated from untreated MSCs and MSCs pretreated with Ba, and were characterized using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Subsequently, Cell Counting Kit-8 and Transwell assays, reverse transcription-quantitative PCR, immunofluorescence, western blotting and ELISA were used to evaluate the effects of Ba-exos on AS, and the possible molecular mechanisms. Oil Red O and Masson staining were used to assess AS pathological tissue in a high-fat diet-induced mouse model of AS. Notably, MSC-exos and Ba-exos were successfully isolated. Compared with MSC-exos, Ba-exos demonstrated superior inhibitory effects on the viability and migration, and the levels of inflammatory factors in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs). Additionally, compared with MSC-exos, Ba-exos significantly inhibited NF-kappa B activation by upregulating sirtuin 1 (SIRT1), thereby suppressing inflammation in ox-LDL-induced VSMCs to a greater extent. In mice with high-fat diet-induced AS, Ba-exos exhibited the ability to inhibit AS plaque formation and to alleviate AS progression by reducing the levels of inflammatory factors compared with MSC-exos; however, the difference was not significant. In conclusion, Ba-exos may serve as a potential strategy for treating AS by regulating the SIRT1/NF-kappa B signaling pathway to suppress inflammation.
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页数:13
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