EPCs-exos combined with tanshinone Ⅱ_A protect vascular endothelium cells from oxidative damage via PI3K/Akt pathway.
10.19540/j.cnki.cjcmm.20230828.701
- Author:
Lu MA
1
;
Lei YANG
2
;
Chang-Qing DENG
1
;
Wei ZHANG
1
;
Huang DING
1
;
Xiao-Dan LIU
1
;
Wan-Yu LI
1
;
Jiang WEN
1
;
Wei TAN
1
;
Yan-Ling LI
1
;
Yan-Yan ZHANG
1
;
Xin-Ying FU
1
;
Lin-Quan LIU
1
;
Cai-Xia LIU
1
;
Zhao-Wen ZENG
2
Author Information
1. College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine Changsha 410208, China Hunan Key Laboratory of Integrated Chinese and Western Medicine for Prevention and Treatment of Heart and Brain Diseases Changsha 410208, China.
2. the First Affiliated Hospital of Hunan University of Chinese Medicine Changsha 410007, China.
- Publication Type:Journal Article
- Keywords:
PI3K/Akt pathway;
coronary heart disease;
endothelial progenitor cells;
exosomes;
tanshinone Ⅱ_A;
vascular endothelial cells
- MeSH:
Proto-Oncogene Proteins c-akt/metabolism*;
Phosphatidylinositol 3-Kinases/metabolism*;
Signal Transduction;
Reactive Oxygen Species/metabolism*;
Tumor Necrosis Factor-alpha/metabolism*;
Interleukin-6/metabolism*;
Endothelium, Vascular;
Oxidative Stress;
Endothelial Progenitor Cells;
RNA, Messenger/metabolism*;
Abietanes
- From:
China Journal of Chinese Materia Medica
2023;48(23):6423-6433
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to investigate the molecular mechanism of tanshinone Ⅱ_(A )(TaⅡ_A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ_A, EPCs-exos, and TaⅡ_A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ_A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ_A+EPCs-exos outperformed TaⅡ_A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ_A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.
