Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway
Background Carboxyl‐terminal modulator protein (CTMP) has been implicated in cancer, brain injury, and obesity. However, the role of CTMP in pathological cardiac hypertrophy has not been identified. Methods and Results In this study, decreased expression of CTMP was observed in both human failing he...
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| Format: | Article |
| Language: | English |
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Wiley
2018-07-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.118.008654 |
| _version_ | 1819178983085834240 |
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| author | Xiaoxiong Liu Qin Yang Li‐Hua Zhu Jia Liu Ke‐Qiong Deng Xue‐Yong Zhu Ye Liu Jun Gong Peng Zhang Shuyan Li Hao Xia Zhi‐Gang She |
| author_facet | Xiaoxiong Liu Qin Yang Li‐Hua Zhu Jia Liu Ke‐Qiong Deng Xue‐Yong Zhu Ye Liu Jun Gong Peng Zhang Shuyan Li Hao Xia Zhi‐Gang She |
| author_sort | Xiaoxiong Liu |
| collection | DOAJ |
| description | Background Carboxyl‐terminal modulator protein (CTMP) has been implicated in cancer, brain injury, and obesity. However, the role of CTMP in pathological cardiac hypertrophy has not been identified. Methods and Results In this study, decreased expression of CTMP was observed in both human failing hearts and murine hypertrophied hearts. To further explore the potential involvement of CTMP in pathological cardiac hypertrophy, cardiac‐specific CTMP knockout and overexpression mice were generated. In vivo experiments revealed that CTMP deficiency exacerbated the cardiac hypertrophy, fibrosis, and function induced by pressure overload, whereas CTMP overexpression alleviated the response to hypertrophic stimuli. Consistent with the in vivo results, adenovirus‐mediated gain‐of‐function or loss‐of‐function experiments showed that CTMP also exerted a protective effect against hypertrophic responses to angiotensin II in vitro. Mechanistically, CTMP ameliorated pathological cardiac hypertrophy through the blockade of the protein kinase B signaling pathway. Moreover, inhibition of protein kinase B activation with LY294002 rescued the deteriorated effect in aortic banding–treated cardiac‐specific CTMP knockout mice. Conclusions Taken together, these findings imply, for the first time, that increasing the cardiac expression of CTMP may be a novel therapeutic strategy for pathological cardiac hypertrophy. |
| first_indexed | 2024-12-22T21:51:13Z |
| format | Article |
| id | doaj.art-88882cacec304168b65de30be4e8ce31 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-22T21:51:13Z |
| publishDate | 2018-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-88882cacec304168b65de30be4e8ce312022-12-21T18:11:22ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802018-07-0171310.1161/JAHA.118.008654Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling PathwayXiaoxiong Liu0Qin Yang1Li‐Hua Zhu2Jia Liu3Ke‐Qiong Deng4Xue‐Yong Zhu5Ye Liu6Jun Gong7Peng Zhang8Shuyan Li9Hao Xia10Zhi‐Gang She11Department of Cardiology Renmin Hospital of Wuhan University Wuhan ChinaMedical Science Research Center Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Cardiology Renmin Hospital of Wuhan University Wuhan ChinaDepartment of Cardiology First Hospital of Jilin University Changchun ChinaDepartment of Cardiology Renmin Hospital of Wuhan University Wuhan ChinaDepartment of Cardiology Renmin Hospital of Wuhan University Wuhan ChinaMedical Science Research Center Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Cardiology Renmin Hospital of Wuhan University Wuhan ChinaMedical Science Research Center Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Cardiology First Hospital of Jilin University Changchun ChinaDepartment of Cardiology Renmin Hospital of Wuhan University Wuhan ChinaDepartment of Cardiology Renmin Hospital of Wuhan University Wuhan ChinaBackground Carboxyl‐terminal modulator protein (CTMP) has been implicated in cancer, brain injury, and obesity. However, the role of CTMP in pathological cardiac hypertrophy has not been identified. Methods and Results In this study, decreased expression of CTMP was observed in both human failing hearts and murine hypertrophied hearts. To further explore the potential involvement of CTMP in pathological cardiac hypertrophy, cardiac‐specific CTMP knockout and overexpression mice were generated. In vivo experiments revealed that CTMP deficiency exacerbated the cardiac hypertrophy, fibrosis, and function induced by pressure overload, whereas CTMP overexpression alleviated the response to hypertrophic stimuli. Consistent with the in vivo results, adenovirus‐mediated gain‐of‐function or loss‐of‐function experiments showed that CTMP also exerted a protective effect against hypertrophic responses to angiotensin II in vitro. Mechanistically, CTMP ameliorated pathological cardiac hypertrophy through the blockade of the protein kinase B signaling pathway. Moreover, inhibition of protein kinase B activation with LY294002 rescued the deteriorated effect in aortic banding–treated cardiac‐specific CTMP knockout mice. Conclusions Taken together, these findings imply, for the first time, that increasing the cardiac expression of CTMP may be a novel therapeutic strategy for pathological cardiac hypertrophy.https://www.ahajournals.org/doi/10.1161/JAHA.118.008654angiotensin IIaortic bandingcarboxyl‐terminal modulator proteinpathological cardiac hypertrophysignal transduction |
| spellingShingle | Xiaoxiong Liu Qin Yang Li‐Hua Zhu Jia Liu Ke‐Qiong Deng Xue‐Yong Zhu Ye Liu Jun Gong Peng Zhang Shuyan Li Hao Xia Zhi‐Gang She Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease angiotensin II aortic banding carboxyl‐terminal modulator protein pathological cardiac hypertrophy signal transduction |
| title | Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway |
| title_full | Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway |
| title_fullStr | Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway |
| title_full_unstemmed | Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway |
| title_short | Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway |
| title_sort | carboxyl terminal modulator protein ameliorates pathological cardiac hypertrophy by suppressing the protein kinase b signaling pathway |
| topic | angiotensin II aortic banding carboxyl‐terminal modulator protein pathological cardiac hypertrophy signal transduction |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.118.008654 |
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