Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria Dysfunction
Thoracic radiotherapy patients have higher risks of developing radiation-induced heart disease (RIHD). Ionizing radiation generates excessive reactive oxygens species (ROS) causing oxidative stress, while Momordica. charantia and its extract have antioxidant activity. Plant-derived extracellular ves...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.864188/full |
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| author | Wen-Wen Cui Cong Ye Kai-Xuan Wang Xu Yang Xu Yang Pei-Yan Zhu Kan Hu Ting Lan Lin-Yan Huang Wan Wang Bing Gu Chen Yan Ping Ma Su-Hua Qi Lan Luo |
| author_facet | Wen-Wen Cui Cong Ye Kai-Xuan Wang Xu Yang Xu Yang Pei-Yan Zhu Kan Hu Ting Lan Lin-Yan Huang Wan Wang Bing Gu Chen Yan Ping Ma Su-Hua Qi Lan Luo |
| author_sort | Wen-Wen Cui |
| collection | DOAJ |
| description | Thoracic radiotherapy patients have higher risks of developing radiation-induced heart disease (RIHD). Ionizing radiation generates excessive reactive oxygens species (ROS) causing oxidative stress, while Momordica. charantia and its extract have antioxidant activity. Plant-derived extracellular vesicles (EVs) is emerging as novel therapeutic agent. Therefore, we explored the protective effects of Momordica. charantia-derived EVs-like nanovesicles (MCELNs) against RIHD. Using density gradient centrifugation, we successfully isolated MCELNs with similar shape, size, and markers as EVs. Confocal imaging revealed that rat cardiomyocytes H9C2 cells internalized PKH67 labeled MCELNs time-dependently. In vitro assay identified that MCELNs promoted cell proliferation, suppressed cell apoptosis, and alleviated the DNA damage in irradiated (16 Gy, X-ray) H9C2 cells. Moreover, elevated mitochondria ROS in irradiated H9C2 cells were scavenged by MCELNs, protecting mitochondria function with re-balanced mitochondria membrane potential. Furthermore, the phosphorylation of ROS-related proteins was recovered with increased ratios of p-AKT/AKT and p-ERK/ERK in MCELNs treated irradiated H9C2 cells. Last, intraperitoneal administration of MCELNs mitigated myocardial injury and fibrosis in a thoracic radiation mice model. Our data demonstrated the potential protective effects of MCELNs against RIHD. The MCELNs shed light on preventive regime development for radiation-related toxicity. |
| first_indexed | 2024-12-10T10:53:23Z |
| format | Article |
| id | doaj.art-20f40213d7f1470baaccdffc8eb74cd9 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-10T10:53:23Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-20f40213d7f1470baaccdffc8eb74cd92022-12-22T01:51:57ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-04-01910.3389/fcvm.2022.864188864188Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria DysfunctionWen-Wen Cui0Cong Ye1Kai-Xuan Wang2Xu Yang3Xu Yang4Pei-Yan Zhu5Kan Hu6Ting Lan7Lin-Yan Huang8Wan Wang9Bing Gu10Chen Yan11Ping Ma12Su-Hua Qi13Lan Luo14Medical Technology School, Xuzhou Medical University, Xuzhou, ChinaMedical Technology School, Xuzhou Medical University, Xuzhou, ChinaMedical Technology School, Xuzhou Medical University, Xuzhou, ChinaMedical Technology School, Xuzhou Medical University, Xuzhou, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaMedical Technology School, Xuzhou Medical University, Xuzhou, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaMedical Technology School, Xuzhou Medical University, Xuzhou, ChinaMedical Technology School, Xuzhou Medical University, Xuzhou, ChinaMedical Technology School, Xuzhou Medical University, Xuzhou, ChinaDepartment of Laboratory Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Rheumatology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaMedical Technology School, Xuzhou Medical University, Xuzhou, ChinaMedical Technology School, Xuzhou Medical University, Xuzhou, ChinaThoracic radiotherapy patients have higher risks of developing radiation-induced heart disease (RIHD). Ionizing radiation generates excessive reactive oxygens species (ROS) causing oxidative stress, while Momordica. charantia and its extract have antioxidant activity. Plant-derived extracellular vesicles (EVs) is emerging as novel therapeutic agent. Therefore, we explored the protective effects of Momordica. charantia-derived EVs-like nanovesicles (MCELNs) against RIHD. Using density gradient centrifugation, we successfully isolated MCELNs with similar shape, size, and markers as EVs. Confocal imaging revealed that rat cardiomyocytes H9C2 cells internalized PKH67 labeled MCELNs time-dependently. In vitro assay identified that MCELNs promoted cell proliferation, suppressed cell apoptosis, and alleviated the DNA damage in irradiated (16 Gy, X-ray) H9C2 cells. Moreover, elevated mitochondria ROS in irradiated H9C2 cells were scavenged by MCELNs, protecting mitochondria function with re-balanced mitochondria membrane potential. Furthermore, the phosphorylation of ROS-related proteins was recovered with increased ratios of p-AKT/AKT and p-ERK/ERK in MCELNs treated irradiated H9C2 cells. Last, intraperitoneal administration of MCELNs mitigated myocardial injury and fibrosis in a thoracic radiation mice model. Our data demonstrated the potential protective effects of MCELNs against RIHD. The MCELNs shed light on preventive regime development for radiation-related toxicity.https://www.frontiersin.org/articles/10.3389/fcvm.2022.864188/fullMomordica. charantia-derived extracellular vesicles-like nanovesiclesradiation-induced heart diseaseDNA damagemitochondria dysfunctionH9C2 cells |
| spellingShingle | Wen-Wen Cui Cong Ye Kai-Xuan Wang Xu Yang Xu Yang Pei-Yan Zhu Kan Hu Ting Lan Lin-Yan Huang Wan Wang Bing Gu Chen Yan Ping Ma Su-Hua Qi Lan Luo Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria Dysfunction Frontiers in Cardiovascular Medicine Momordica. charantia-derived extracellular vesicles-like nanovesicles radiation-induced heart disease DNA damage mitochondria dysfunction H9C2 cells |
| title | Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria Dysfunction |
| title_full | Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria Dysfunction |
| title_fullStr | Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria Dysfunction |
| title_full_unstemmed | Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria Dysfunction |
| title_short | Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria Dysfunction |
| title_sort | momordica charantia derived extracellular vesicles like nanovesicles protect cardiomyocytes against radiation injury via attenuating dna damage and mitochondria dysfunction |
| topic | Momordica. charantia-derived extracellular vesicles-like nanovesicles radiation-induced heart disease DNA damage mitochondria dysfunction H9C2 cells |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.864188/full |
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