Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis
Abstract Objectives This study aimed to determine the effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-EXO) on atherosclerosis (AS), and its related underlying mechanisms. Methods Exosomes were isolated from mouse BMSCs, and identified by transmission electron microscopy...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-09-01
|
| Series: | BMC Cardiovascular Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12872-023-03453-y |
| _version_ | 1797453961376038912 |
|---|---|
| author | Zhibin Bai Haolin Hu Fangfang Hu Jiajie Ji Zhenling Ji |
| author_facet | Zhibin Bai Haolin Hu Fangfang Hu Jiajie Ji Zhenling Ji |
| author_sort | Zhibin Bai |
| collection | DOAJ |
| description | Abstract Objectives This study aimed to determine the effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-EXO) on atherosclerosis (AS), and its related underlying mechanisms. Methods Exosomes were isolated from mouse BMSCs, and identified by transmission electron microscopy (TEM), Nanosight (NTA), and western blot. A mouse AS model was established, and exosomes were injected into the tail vein. Total cholesterol (TC) and triglycerides (TG) were detected using their corresponding assay kits. The contents of IL-1β and IL-18 in serum were detected by ELISA. The mRNA and protein expression levels of GSDMD, Caspase1, and NLRP3 were detected by qRT-PCR and Western blot. Finally, aortic tissues in the Model and BMSC-EXO groups were sent for sequencing. Results TEM, NTA, and western blot indicated successful isolation of exosomes. Compared with the control group, the TC, TG contents, IL-1β and IL-18 concentrations of the mice in the Model group were significantly increased; nonetheless, were significantly lower after injected with BMSC-EXO than those in the Model group (p < 0.05). Compared with the control group, the expressions of NLRP3, caspase-1 and GSDMD were significantly up-regulated in the Model group (p < 0.05), while the expressions of NLRP3, caspase-1, and GSDMD were significantly down-regulated by BMSC-EXO. By sequencing, a total of 3852 DEGs were identified between the Model and BMSC-EXO group and were significantly enriched in various biological processes and pathways related to mitochondrial function, metabolism, inflammation, and immune response. Conclusion AS can induce pyroptosis, and BMSC-EXO can reduce inflammation and alleviate the progression of AS by inhibiting NLRP3/Caspase-1/GSDMD in the pyroptosis pathway. |
| first_indexed | 2024-03-09T15:30:27Z |
| format | Article |
| id | doaj.art-a6e5d1e6694b42b3a2e7b3047328eef0 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-03-09T15:30:27Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-a6e5d1e6694b42b3a2e7b3047328eef02023-11-26T12:16:46ZengBMCBMC Cardiovascular Disorders1471-22612023-09-0123111410.1186/s12872-023-03453-yBone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosisZhibin Bai0Haolin Hu1Fangfang Hu2Jiajie Ji3Zhenling Ji4Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Medical School, Zhongda Hospital, Southeast UniversityDepartment of General Surgery, Institute for Minimally Invasive Surgery, Medical School, ZhongDa Hospital, Southeast UniversityDepartment of General Surgery, Institute for Minimally Invasive Surgery, Medical School, ZhongDa Hospital, Southeast UniversityCenter of Interventional Radiology and Vascular Surgery, Department of Radiology, Medical School, Zhongda Hospital, Southeast UniversityDepartment of General Surgery, Institute for Minimally Invasive Surgery, Medical School, ZhongDa Hospital, Southeast UniversityAbstract Objectives This study aimed to determine the effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-EXO) on atherosclerosis (AS), and its related underlying mechanisms. Methods Exosomes were isolated from mouse BMSCs, and identified by transmission electron microscopy (TEM), Nanosight (NTA), and western blot. A mouse AS model was established, and exosomes were injected into the tail vein. Total cholesterol (TC) and triglycerides (TG) were detected using their corresponding assay kits. The contents of IL-1β and IL-18 in serum were detected by ELISA. The mRNA and protein expression levels of GSDMD, Caspase1, and NLRP3 were detected by qRT-PCR and Western blot. Finally, aortic tissues in the Model and BMSC-EXO groups were sent for sequencing. Results TEM, NTA, and western blot indicated successful isolation of exosomes. Compared with the control group, the TC, TG contents, IL-1β and IL-18 concentrations of the mice in the Model group were significantly increased; nonetheless, were significantly lower after injected with BMSC-EXO than those in the Model group (p < 0.05). Compared with the control group, the expressions of NLRP3, caspase-1 and GSDMD were significantly up-regulated in the Model group (p < 0.05), while the expressions of NLRP3, caspase-1, and GSDMD were significantly down-regulated by BMSC-EXO. By sequencing, a total of 3852 DEGs were identified between the Model and BMSC-EXO group and were significantly enriched in various biological processes and pathways related to mitochondrial function, metabolism, inflammation, and immune response. Conclusion AS can induce pyroptosis, and BMSC-EXO can reduce inflammation and alleviate the progression of AS by inhibiting NLRP3/Caspase-1/GSDMD in the pyroptosis pathway.https://doi.org/10.1186/s12872-023-03453-yAtherosclerosisBone marrow mesenchymal stem cellsExosomesPyroptosis |
| spellingShingle | Zhibin Bai Haolin Hu Fangfang Hu Jiajie Ji Zhenling Ji Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis BMC Cardiovascular Disorders Atherosclerosis Bone marrow mesenchymal stem cells Exosomes Pyroptosis |
| title | Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis |
| title_full | Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis |
| title_fullStr | Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis |
| title_full_unstemmed | Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis |
| title_short | Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis |
| title_sort | bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis |
| topic | Atherosclerosis Bone marrow mesenchymal stem cells Exosomes Pyroptosis |
| url | https://doi.org/10.1186/s12872-023-03453-y |
| work_keys_str_mv | AT zhibinbai bonemarrowmesenchymalstemcellsderivedexosomesstabilizeatherosclerosisthroughinhibitingpyroptosis AT haolinhu bonemarrowmesenchymalstemcellsderivedexosomesstabilizeatherosclerosisthroughinhibitingpyroptosis AT fangfanghu bonemarrowmesenchymalstemcellsderivedexosomesstabilizeatherosclerosisthroughinhibitingpyroptosis AT jiajieji bonemarrowmesenchymalstemcellsderivedexosomesstabilizeatherosclerosisthroughinhibitingpyroptosis AT zhenlingji bonemarrowmesenchymalstemcellsderivedexosomesstabilizeatherosclerosisthroughinhibitingpyroptosis |