Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury
Objective: Extracellular vesicles (EVs) have garnered considerable attention among researchers as candidates for natural drug delivery systems. This study aimed to investigate whether extracellular vesicle mediated targeting delivery of growth differentiation factor-15 (GDF15) improves myocardial re...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224001057 |
| _version_ | 1797291859272269824 |
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| author | Tingting Xiao Jun Wei Dabei Cai Yu Wang Zhiwei Cui Qianwen Chen Qingqing Gu Ailin Zou Lipeng Mao Boyu Chi Yuan Ji Qingjie Wang Ling Sun |
| author_facet | Tingting Xiao Jun Wei Dabei Cai Yu Wang Zhiwei Cui Qianwen Chen Qingqing Gu Ailin Zou Lipeng Mao Boyu Chi Yuan Ji Qingjie Wang Ling Sun |
| author_sort | Tingting Xiao |
| collection | DOAJ |
| description | Objective: Extracellular vesicles (EVs) have garnered considerable attention among researchers as candidates for natural drug delivery systems. This study aimed to investigate whether extracellular vesicle mediated targeting delivery of growth differentiation factor-15 (GDF15) improves myocardial repair by reprogramming macrophages post myocardial injury. Methods: EVs were isolated from macrophages transfected with GDF15 (EXO-GDF15) and control macrophages (EXO-NC). In vitro and vivo experiments, we compared their reprogram ability of macrophages and regeneration activity. Furthermore, proteomic analysis were employed to determine the specific mechanism by which GDF15 repairs the myocardium. Results: Compared with EXO-NC, EXO-GDF15 significantly regulated macrophage phenotypic shift, inhibited cardiomyocyte apoptosis, and enhanced endothelial cell angiogenesis. Moreover, EXO-GDF15 also significantly regulated macrophage heterogeneity and inflammatory cytokines, reduced fibrotic area, and enhanced cardiac function in infarcted rats. Proteomic analysis revealed a decrease in fatty acid-binding protein 4 (FABP4) protein expression following treatment with EXO-GDF15. Mechanistically, the reprogramming of macrophages by EXO-GDF15 is accomplished through the activation of Smad2/3 phosphorylation, which subsequently inhibits the production of FABP4. Conclusions: Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury via down-regulating the expression of FABP4. EXO-GDF15 may serve as a promising approach of immunotherapy. |
| first_indexed | 2024-03-07T19:43:50Z |
| format | Article |
| id | doaj.art-ce2ee1ce770c4eaeb43d3cebdd25bb67 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-07T19:43:50Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-ce2ee1ce770c4eaeb43d3cebdd25bb672024-02-29T05:17:47ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-03-01172116224Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injuryTingting Xiao0Jun Wei1Dabei Cai2Yu Wang3Zhiwei Cui4Qianwen Chen5Qingqing Gu6Ailin Zou7Lipeng Mao8Boyu Chi9Yuan Ji10Qingjie Wang11Ling Sun12Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, ChinaDepartment of Cardiovascular Surgery, the First Affiliated Hospital of Wannan Medical College, Wuhu 241000, Anhui, ChinaDepartment of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, ChinaDepartment of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, ChinaDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, ChinaDepartment of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, ChinaDepartment of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, ChinaDepartment of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China; Dalian Medical University, Dalian 116000, Liaoning, ChinaDepartment of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China; Dalian Medical University, Dalian 116000, Liaoning, ChinaDepartment of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China; Corresponding authors at: Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China.Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China; Corresponding authors at: Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China.Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China; Dalian Medical University, Dalian 116000, Liaoning, China; Corresponding authors at: Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China.Objective: Extracellular vesicles (EVs) have garnered considerable attention among researchers as candidates for natural drug delivery systems. This study aimed to investigate whether extracellular vesicle mediated targeting delivery of growth differentiation factor-15 (GDF15) improves myocardial repair by reprogramming macrophages post myocardial injury. Methods: EVs were isolated from macrophages transfected with GDF15 (EXO-GDF15) and control macrophages (EXO-NC). In vitro and vivo experiments, we compared their reprogram ability of macrophages and regeneration activity. Furthermore, proteomic analysis were employed to determine the specific mechanism by which GDF15 repairs the myocardium. Results: Compared with EXO-NC, EXO-GDF15 significantly regulated macrophage phenotypic shift, inhibited cardiomyocyte apoptosis, and enhanced endothelial cell angiogenesis. Moreover, EXO-GDF15 also significantly regulated macrophage heterogeneity and inflammatory cytokines, reduced fibrotic area, and enhanced cardiac function in infarcted rats. Proteomic analysis revealed a decrease in fatty acid-binding protein 4 (FABP4) protein expression following treatment with EXO-GDF15. Mechanistically, the reprogramming of macrophages by EXO-GDF15 is accomplished through the activation of Smad2/3 phosphorylation, which subsequently inhibits the production of FABP4. Conclusions: Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury via down-regulating the expression of FABP4. EXO-GDF15 may serve as a promising approach of immunotherapy.http://www.sciencedirect.com/science/article/pii/S0753332224001057GDF-15Extracellular vesiclesFABP4Acute myocardial infarction |
| spellingShingle | Tingting Xiao Jun Wei Dabei Cai Yu Wang Zhiwei Cui Qianwen Chen Qingqing Gu Ailin Zou Lipeng Mao Boyu Chi Yuan Ji Qingjie Wang Ling Sun Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury Biomedicine & Pharmacotherapy GDF-15 Extracellular vesicles FABP4 Acute myocardial infarction |
| title | Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury |
| title_full | Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury |
| title_fullStr | Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury |
| title_full_unstemmed | Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury |
| title_short | Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury |
| title_sort | extracellular vesicle mediated targeting delivery of growth differentiation factor 15 improves myocardial repair by reprogramming macrophages post myocardial injury |
| topic | GDF-15 Extracellular vesicles FABP4 Acute myocardial infarction |
| url | http://www.sciencedirect.com/science/article/pii/S0753332224001057 |
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