Angiotensin‐Converting Enzyme 3 (ACE3) Protects Against Pressure Overload‐Induced Cardiac Hypertrophy
BackgroundAngiotensin‐converting enzyme 3 (ACE3) is a recently defined homolog of ACE. However, the pathophysiological function of ACE3 is largely unknown. Here, we aim to explore the role of ACE3 in pathological cardiac hypertrophy. Methods and ResultsNeonatal rat cardiomyocytes (NRCMs) with gain a...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-02-01
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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.115.002680 |
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| author | Chang‐Jiang Yu Liang‐Liang Tang Chen Liang Xiao Chen Shu‐Ying Song Xiao‐Qing Ding Kun‐Yu Zhang Bin‐Lin Song Dan Zhao Xue‐Yong Zhu Hong‐Liang Li Zhi‐Ren Zhang |
| author_facet | Chang‐Jiang Yu Liang‐Liang Tang Chen Liang Xiao Chen Shu‐Ying Song Xiao‐Qing Ding Kun‐Yu Zhang Bin‐Lin Song Dan Zhao Xue‐Yong Zhu Hong‐Liang Li Zhi‐Ren Zhang |
| author_sort | Chang‐Jiang Yu |
| collection | DOAJ |
| description | BackgroundAngiotensin‐converting enzyme 3 (ACE3) is a recently defined homolog of ACE. However, the pathophysiological function of ACE3 is largely unknown. Here, we aim to explore the role of ACE3 in pathological cardiac hypertrophy. Methods and ResultsNeonatal rat cardiomyocytes (NRCMs) with gain and loss of function of ACE3 and mice with global knockout or cardiac‐specific overexpression of ACE3 were used in this study. In cultured cardiomyocytes, ACE3 conferred protection against angiotensin II (Ang II)‐induced hypertrophic growth. Cardiac hypertrophy in mice was induced by aortic banding (AB) and the extent of hypertrophy was analyzed through echocardiographic, pathological, and molecular analyses. Our data demonstrated that ACE3‐deficient mice exhibited more pronounced cardiac hypertrophy and fibrosis and a strong decrease in cardiac contractile function, conversely, cardiac‐specific ACE3‐overexpressing mice displayed an attenuated hypertrophic phenotype, compared with control mice, respectively. Analyses of the underlying molecular mechanism revealed that ACE3‐mediated protection against cardiac hypertrophy by suppressing the activation of mitogen‐activated protein kinase kinase (MEK)‐regulated extracellular signal‐regulated protein kinase (ERK1/2) signaling, which was further evidenced by the observation that inhibition of the MEK‐ERK1/2 signaling by U0126 rescued the exacerbated hypertrophic phenotype in ACE3‐deficient mice. ConclusionsOur comprehensive analyses suggest that ACE3 inhibits pressure overload‐induced cardiac hypertrophy by blocking the MEK‐ERK1/2 signaling pathway. |
| first_indexed | 2024-04-13T15:35:50Z |
| format | Article |
| id | doaj.art-c4c39db23a9d4c7a884f4290fad394c5 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-13T15:35:50Z |
| publishDate | 2016-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c4c39db23a9d4c7a884f4290fad394c52022-12-22T02:41:17ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-02-015210.1161/JAHA.115.002680Angiotensin‐Converting Enzyme 3 (ACE3) Protects Against Pressure Overload‐Induced Cardiac HypertrophyChang‐Jiang Yu0Liang‐Liang Tang1Chen Liang2Xiao Chen3Shu‐Ying Song4Xiao‐Qing Ding5Kun‐Yu Zhang6Bin‐Lin Song7Dan Zhao8Xue‐Yong Zhu9Hong‐Liang Li10Zhi‐Ren Zhang11Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, ChinaHarbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, ChinaHarbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, ChinaHarbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, ChinaHarbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, ChinaHarbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, ChinaHarbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, ChinaHarbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, ChinaKey Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHarbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, ChinaBackgroundAngiotensin‐converting enzyme 3 (ACE3) is a recently defined homolog of ACE. However, the pathophysiological function of ACE3 is largely unknown. Here, we aim to explore the role of ACE3 in pathological cardiac hypertrophy. Methods and ResultsNeonatal rat cardiomyocytes (NRCMs) with gain and loss of function of ACE3 and mice with global knockout or cardiac‐specific overexpression of ACE3 were used in this study. In cultured cardiomyocytes, ACE3 conferred protection against angiotensin II (Ang II)‐induced hypertrophic growth. Cardiac hypertrophy in mice was induced by aortic banding (AB) and the extent of hypertrophy was analyzed through echocardiographic, pathological, and molecular analyses. Our data demonstrated that ACE3‐deficient mice exhibited more pronounced cardiac hypertrophy and fibrosis and a strong decrease in cardiac contractile function, conversely, cardiac‐specific ACE3‐overexpressing mice displayed an attenuated hypertrophic phenotype, compared with control mice, respectively. Analyses of the underlying molecular mechanism revealed that ACE3‐mediated protection against cardiac hypertrophy by suppressing the activation of mitogen‐activated protein kinase kinase (MEK)‐regulated extracellular signal‐regulated protein kinase (ERK1/2) signaling, which was further evidenced by the observation that inhibition of the MEK‐ERK1/2 signaling by U0126 rescued the exacerbated hypertrophic phenotype in ACE3‐deficient mice. ConclusionsOur comprehensive analyses suggest that ACE3 inhibits pressure overload‐induced cardiac hypertrophy by blocking the MEK‐ERK1/2 signaling pathway.https://www.ahajournals.org/doi/10.1161/JAHA.115.002680angiotensin‐converting enzyme 3cardiac hypertrophyERK1/2MEK1/2signaling pathway |
| spellingShingle | Chang‐Jiang Yu Liang‐Liang Tang Chen Liang Xiao Chen Shu‐Ying Song Xiao‐Qing Ding Kun‐Yu Zhang Bin‐Lin Song Dan Zhao Xue‐Yong Zhu Hong‐Liang Li Zhi‐Ren Zhang Angiotensin‐Converting Enzyme 3 (ACE3) Protects Against Pressure Overload‐Induced Cardiac Hypertrophy Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease angiotensin‐converting enzyme 3 cardiac hypertrophy ERK1/2 MEK1/2 signaling pathway |
| title | Angiotensin‐Converting Enzyme 3 (ACE3) Protects Against Pressure Overload‐Induced Cardiac Hypertrophy |
| title_full | Angiotensin‐Converting Enzyme 3 (ACE3) Protects Against Pressure Overload‐Induced Cardiac Hypertrophy |
| title_fullStr | Angiotensin‐Converting Enzyme 3 (ACE3) Protects Against Pressure Overload‐Induced Cardiac Hypertrophy |
| title_full_unstemmed | Angiotensin‐Converting Enzyme 3 (ACE3) Protects Against Pressure Overload‐Induced Cardiac Hypertrophy |
| title_short | Angiotensin‐Converting Enzyme 3 (ACE3) Protects Against Pressure Overload‐Induced Cardiac Hypertrophy |
| title_sort | angiotensin converting enzyme 3 ace3 protects against pressure overload induced cardiac hypertrophy |
| topic | angiotensin‐converting enzyme 3 cardiac hypertrophy ERK1/2 MEK1/2 signaling pathway |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.115.002680 |
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