AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo
Abstract Cardiac hypertrophy is one of the most common genetic heart disorders and considered a risk factor for cardiac morbidity and mortality. The mammalian target of rapamycin (mTOR) pathway plays a key regulatory function in cardiovascular physiology and pathology in hypertrophy. AZD2014 is a sm...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-10-01
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| Series: | Journal of Biological Engineering |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13036-021-00276-3 |
| _version_ | 1819024190647304192 |
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| author | Byung-Hyun Cha Minjin Jung Angela S. Kim Victoria C. Lepak Brett A. Colson David A. Bull Youngwook Won |
| author_facet | Byung-Hyun Cha Minjin Jung Angela S. Kim Victoria C. Lepak Brett A. Colson David A. Bull Youngwook Won |
| author_sort | Byung-Hyun Cha |
| collection | DOAJ |
| description | Abstract Cardiac hypertrophy is one of the most common genetic heart disorders and considered a risk factor for cardiac morbidity and mortality. The mammalian target of rapamycin (mTOR) pathway plays a key regulatory function in cardiovascular physiology and pathology in hypertrophy. AZD2014 is a small-molecule ATP competitive mTOR inhibitor working on both mTORC1 and mTORC2 complexes. Little is known about the therapeutic effects of AZD2014 in cardiac hypertrophy and its underlying mechanism. Here, AZD2014 is examined in in vitro model of phenylephrine (PE)-induced human cardiomyocyte hypertrophy and a myosin-binding protein-C (Mybpc3)-targeted knockout (KO) mouse model of cardiac hypertrophy. Our results demonstrate that cardiomyocytes treated with AZD2014 retain the normal phenotype and AZD2014 attenuates cardiac hypertrophy in the Mybpc3-KO mouse model through inhibition of dual mTORC1 and mTORC2, which in turn results in the down-regulation of the Akt/mTOR signaling pathway. |
| first_indexed | 2024-12-21T04:50:51Z |
| format | Article |
| id | doaj.art-9b0e98c8331144218e05212cc539892d |
| institution | Directory Open Access Journal |
| issn | 1754-1611 |
| language | English |
| last_indexed | 2024-12-21T04:50:51Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biological Engineering |
| spelling | doaj.art-9b0e98c8331144218e05212cc539892d2022-12-21T19:15:26ZengBMCJournal of Biological Engineering1754-16112021-10-0115111010.1186/s13036-021-00276-3AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivoByung-Hyun Cha0Minjin Jung1Angela S. Kim2Victoria C. Lepak3Brett A. Colson4David A. Bull5Youngwook Won6Division of Cardio-Thoracic Surgery, Department of Surgery, University of Arizona College of MedicineDivision of Cardio-Thoracic Surgery, Department of Surgery, University of Arizona College of MedicineDivision of Cardio-Thoracic Surgery, Department of Surgery, University of Arizona College of MedicineDepartment of Cellular & Molecular Medicine, University of Arizona College of MedicineDepartment of Cellular & Molecular Medicine, University of Arizona College of MedicineDivision of Cardio-Thoracic Surgery, Department of Surgery, University of Arizona College of MedicineDivision of Cardio-Thoracic Surgery, Department of Surgery, University of Arizona College of MedicineAbstract Cardiac hypertrophy is one of the most common genetic heart disorders and considered a risk factor for cardiac morbidity and mortality. The mammalian target of rapamycin (mTOR) pathway plays a key regulatory function in cardiovascular physiology and pathology in hypertrophy. AZD2014 is a small-molecule ATP competitive mTOR inhibitor working on both mTORC1 and mTORC2 complexes. Little is known about the therapeutic effects of AZD2014 in cardiac hypertrophy and its underlying mechanism. Here, AZD2014 is examined in in vitro model of phenylephrine (PE)-induced human cardiomyocyte hypertrophy and a myosin-binding protein-C (Mybpc3)-targeted knockout (KO) mouse model of cardiac hypertrophy. Our results demonstrate that cardiomyocytes treated with AZD2014 retain the normal phenotype and AZD2014 attenuates cardiac hypertrophy in the Mybpc3-KO mouse model through inhibition of dual mTORC1 and mTORC2, which in turn results in the down-regulation of the Akt/mTOR signaling pathway.https://doi.org/10.1186/s13036-021-00276-3AZD2014CardiomyocyteCardiac hypertrophymTOR inhibitor |
| spellingShingle | Byung-Hyun Cha Minjin Jung Angela S. Kim Victoria C. Lepak Brett A. Colson David A. Bull Youngwook Won AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo Journal of Biological Engineering AZD2014 Cardiomyocyte Cardiac hypertrophy mTOR inhibitor |
| title | AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo |
| title_full | AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo |
| title_fullStr | AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo |
| title_full_unstemmed | AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo |
| title_short | AZD2014, a dual mTOR inhibitor, attenuates cardiac hypertrophy in vitro and in vivo |
| title_sort | azd2014 a dual mtor inhibitor attenuates cardiac hypertrophy in vitro and in vivo |
| topic | AZD2014 Cardiomyocyte Cardiac hypertrophy mTOR inhibitor |
| url | https://doi.org/10.1186/s13036-021-00276-3 |
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