Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy
Abstract Background Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM). Methods We explored whether up-regulating autophagy could improve card...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-020-01365-9 |
| _version_ | 1818623336969666560 |
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| author | Bo Jin Haiming Shi Jun Zhu Bangwei Wu Quzhen Geshang |
| author_facet | Bo Jin Haiming Shi Jun Zhu Bangwei Wu Quzhen Geshang |
| author_sort | Bo Jin |
| collection | DOAJ |
| description | Abstract Background Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM). Methods We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms. Results Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82% vs 14.38 ± 1.24%, P < 0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48% vs 45.29 ± 6.68%, P < 0.01; 26.89 ± 4.04% vs 22.17 ± 2.82%, P < 0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice. Conclusions The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM. |
| first_indexed | 2024-12-16T18:39:27Z |
| format | Article |
| id | doaj.art-ff60d7e527ec40a4af07a4311972eee6 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-12-16T18:39:27Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-ff60d7e527ec40a4af07a4311972eee62022-12-21T22:21:06ZengBMCBMC Cardiovascular Disorders1471-22612020-02-012011710.1186/s12872-020-01365-9Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathyBo Jin0Haiming Shi1Jun Zhu2Bangwei Wu3Quzhen Geshang4Department of Cardiology, Huashan Hospital, Fudan UniversityDepartment of Cardiology, Huashan Hospital, Fudan UniversityDepartment of Cardiology, Huashan Hospital, Fudan UniversityDepartment of Cardiology, Huashan Hospital, Fudan UniversityDepartment of Medicine, Medical College of Tibet UniversityAbstract Background Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM). Methods We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms. Results Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82% vs 14.38 ± 1.24%, P < 0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48% vs 45.29 ± 6.68%, P < 0.01; 26.89 ± 4.04% vs 22.17 ± 2.82%, P < 0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice. Conclusions The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.https://doi.org/10.1186/s12872-020-01365-9AutophagymTORCardiac functionDilated cardiomyopathy |
| spellingShingle | Bo Jin Haiming Shi Jun Zhu Bangwei Wu Quzhen Geshang Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy BMC Cardiovascular Disorders Autophagy mTOR Cardiac function Dilated cardiomyopathy |
| title | Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy |
| title_full | Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy |
| title_fullStr | Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy |
| title_full_unstemmed | Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy |
| title_short | Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy |
| title_sort | up regulating autophagy by targeting the mtor 4ebp1 pathway a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy |
| topic | Autophagy mTOR Cardiac function Dilated cardiomyopathy |
| url | https://doi.org/10.1186/s12872-020-01365-9 |
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