Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKT
Abstract Background Doxorubicin (DOX) has limited chemotherapy application for malignancies due to cardiotoxicity. The pathogenesis of DOX-induced cardiomyopathy (DiCM) is yet to be elucidated. Increasing studies proved that activation of AKT prevented cardiomyocyte apoptosis and cardiac dysfunction...
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | BMC Cardiovascular Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12872-022-02517-9 |
| _version_ | 1818919667270418432 |
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| author | Yu Qi Jianzhou Chen Junfeng Duan Lina Kang Kun Wang Ziwei Chen Biao Xu Rong Gu |
| author_facet | Yu Qi Jianzhou Chen Junfeng Duan Lina Kang Kun Wang Ziwei Chen Biao Xu Rong Gu |
| author_sort | Yu Qi |
| collection | DOAJ |
| description | Abstract Background Doxorubicin (DOX) has limited chemotherapy application for malignancies due to cardiotoxicity. The pathogenesis of DOX-induced cardiomyopathy (DiCM) is yet to be elucidated. Increasing studies proved that activation of AKT prevented cardiomyocyte apoptosis and cardiac dysfunction in response to DOX insult. Our previous studies indicated that major vault protein (MVP) deficiency was accompanied by suppressed phosphorylation of AKT in metabolic diseases. This study aimed to investigate the role and underlying mechanism of MVP on cardiomyocyte apoptosis in DiCM. Methods Mice were intraperitoneally injected with DOX 5 mg/kg, once a week for 5 weeks, the total cumulative dose was 25 mg/kg. Cardiomyocyte-specific MVP overexpression was achieved using an adeno-associated virus system under the cTnT promoter after the fourth DOX injection. Cardiac function was examined by echocardiography followed by euthanasia. Tissue and serum were collected for morphology analysis and biochemical examination. Results Herein, we found that MVP expression was upregulated in DOX-treated murine hearts. Cardiac-specific MVP overexpression alleviated DOX-induced cardiac dysfunction, oxidative stress and fibrosis. Mechanistically, MVP overexpression activated AKT signaling and decreased cardiomyocyte apoptosis in DiCM. Conclusions Based on these findings, we supposed that MVP was a potential therapeutic agent against DiCM. |
| first_indexed | 2024-12-20T01:09:30Z |
| format | Article |
| id | doaj.art-a1a262ecc80146d6aeb48f949f3a1a33 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-12-20T01:09:30Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-a1a262ecc80146d6aeb48f949f3a1a332022-12-21T19:58:43ZengBMCBMC Cardiovascular Disorders1471-22612022-03-0122111110.1186/s12872-022-02517-9Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKTYu Qi0Jianzhou Chen1Junfeng Duan2Lina Kang3Kun Wang4Ziwei Chen5Biao Xu6Rong Gu7Department of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Affiliated Hospital of Nantong UniversityDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical SchoolAbstract Background Doxorubicin (DOX) has limited chemotherapy application for malignancies due to cardiotoxicity. The pathogenesis of DOX-induced cardiomyopathy (DiCM) is yet to be elucidated. Increasing studies proved that activation of AKT prevented cardiomyocyte apoptosis and cardiac dysfunction in response to DOX insult. Our previous studies indicated that major vault protein (MVP) deficiency was accompanied by suppressed phosphorylation of AKT in metabolic diseases. This study aimed to investigate the role and underlying mechanism of MVP on cardiomyocyte apoptosis in DiCM. Methods Mice were intraperitoneally injected with DOX 5 mg/kg, once a week for 5 weeks, the total cumulative dose was 25 mg/kg. Cardiomyocyte-specific MVP overexpression was achieved using an adeno-associated virus system under the cTnT promoter after the fourth DOX injection. Cardiac function was examined by echocardiography followed by euthanasia. Tissue and serum were collected for morphology analysis and biochemical examination. Results Herein, we found that MVP expression was upregulated in DOX-treated murine hearts. Cardiac-specific MVP overexpression alleviated DOX-induced cardiac dysfunction, oxidative stress and fibrosis. Mechanistically, MVP overexpression activated AKT signaling and decreased cardiomyocyte apoptosis in DiCM. Conclusions Based on these findings, we supposed that MVP was a potential therapeutic agent against DiCM.https://doi.org/10.1186/s12872-022-02517-9Doxorubicin-induced cardiomyopathyMajor vault proteinAKTApoptosis |
| spellingShingle | Yu Qi Jianzhou Chen Junfeng Duan Lina Kang Kun Wang Ziwei Chen Biao Xu Rong Gu Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKT BMC Cardiovascular Disorders Doxorubicin-induced cardiomyopathy Major vault protein AKT Apoptosis |
| title | Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKT |
| title_full | Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKT |
| title_fullStr | Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKT |
| title_full_unstemmed | Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKT |
| title_short | Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKT |
| title_sort | major vault protein attenuates cardiomyocyte injury in doxorubicin induced cardiomyopathy through activating akt |
| topic | Doxorubicin-induced cardiomyopathy Major vault protein AKT Apoptosis |
| url | https://doi.org/10.1186/s12872-022-02517-9 |
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