Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis
BackgroundEmerging evidence indicates that impaired angiogenesis may contribute to hypertension‐induced cardiac remodeling. The nicotinamide adenine dinucleotide–dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-08-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.117.006114 |
| _version_ | 1819178111181258752 |
|---|---|
| author | Tong Wei Gaojian Huang Jing Gao Chenglin Huang Mengwei Sun Jian Wu Juan Bu Weili Shen |
| author_facet | Tong Wei Gaojian Huang Jing Gao Chenglin Huang Mengwei Sun Jian Wu Juan Bu Weili Shen |
| author_sort | Tong Wei |
| collection | DOAJ |
| description | BackgroundEmerging evidence indicates that impaired angiogenesis may contribute to hypertension‐induced cardiac remodeling. The nicotinamide adenine dinucleotide–dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3‐mediated angiogenesis and cardiac remodeling. Methods and ResultsOur experiments were performed on SIRT3 knockout and age‐matched wild‐type mice infused with angiotensin II (1400 ng/kg per minute) or saline for 14 days. After angiotensin II infusion, SIRT3 knockout mice developed more severe microvascular rarefaction and functional hypoxia in cardiac tissues compared with wild‐type mice. These events were concomitant with mitochondrial dysfunction and enhanced collagen I and collagen III expression, leading to cardiac fibrosis. Silencing SIRT3 facilitated angiotensin II–induced aberrant Pink/Parkin acetylation and impaired mitophagy, while excessive mitochondrial reactive oxygen species generation limited angiogenic capacity in primary mouse cardiac microvascular endothelial cells. Moreover, SIRT3 overexpression in cardiac microvascular endothelial cells enhanced Pink/Parkin‐mediated mitophagy, attenuated mitochondrial reactive oxygen species generation, and restored vessel sprouting and tube formation. In parallel, endothelial cell–specific SIRT3 transgenic mice showed decreased fibrosis, as well as improved cardiac function and microvascular network, compared with wild‐type mice with similar stimuli. ConclusionsCollectively, these findings suggest that SIRT3 could promote angiogenesis through attenuating mitochondrial dysfunction caused by defective mitophagy. |
| first_indexed | 2024-12-22T21:37:21Z |
| format | Article |
| id | doaj.art-63f7143300c34a70b19c525948abc003 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-22T21:37:21Z |
| publishDate | 2017-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-63f7143300c34a70b19c525948abc0032022-12-21T18:11:42ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802017-08-016810.1161/JAHA.117.006114Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing AngiogenesisTong Wei0Gaojian Huang1Jing Gao2Chenglin Huang3Mengwei Sun4Jian Wu5Juan Bu6Weili Shen7State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaState Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaState Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaState Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaKey Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaDepartment of Macromolecular Science, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaBackgroundEmerging evidence indicates that impaired angiogenesis may contribute to hypertension‐induced cardiac remodeling. The nicotinamide adenine dinucleotide–dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3‐mediated angiogenesis and cardiac remodeling. Methods and ResultsOur experiments were performed on SIRT3 knockout and age‐matched wild‐type mice infused with angiotensin II (1400 ng/kg per minute) or saline for 14 days. After angiotensin II infusion, SIRT3 knockout mice developed more severe microvascular rarefaction and functional hypoxia in cardiac tissues compared with wild‐type mice. These events were concomitant with mitochondrial dysfunction and enhanced collagen I and collagen III expression, leading to cardiac fibrosis. Silencing SIRT3 facilitated angiotensin II–induced aberrant Pink/Parkin acetylation and impaired mitophagy, while excessive mitochondrial reactive oxygen species generation limited angiogenic capacity in primary mouse cardiac microvascular endothelial cells. Moreover, SIRT3 overexpression in cardiac microvascular endothelial cells enhanced Pink/Parkin‐mediated mitophagy, attenuated mitochondrial reactive oxygen species generation, and restored vessel sprouting and tube formation. In parallel, endothelial cell–specific SIRT3 transgenic mice showed decreased fibrosis, as well as improved cardiac function and microvascular network, compared with wild‐type mice with similar stimuli. ConclusionsCollectively, these findings suggest that SIRT3 could promote angiogenesis through attenuating mitochondrial dysfunction caused by defective mitophagy.https://www.ahajournals.org/doi/10.1161/JAHA.117.006114angiogenesiscardiac remodelingmitochondriamitophagyoxidative stressSirtuin 3 |
| spellingShingle | Tong Wei Gaojian Huang Jing Gao Chenglin Huang Mengwei Sun Jian Wu Juan Bu Weili Shen Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease angiogenesis cardiac remodeling mitochondria mitophagy oxidative stress Sirtuin 3 |
| title | Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis |
| title_full | Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis |
| title_fullStr | Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis |
| title_full_unstemmed | Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis |
| title_short | Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis |
| title_sort | sirtuin 3 deficiency accelerates hypertensive cardiac remodeling by impairing angiogenesis |
| topic | angiogenesis cardiac remodeling mitochondria mitophagy oxidative stress Sirtuin 3 |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.117.006114 |
| work_keys_str_mv | AT tongwei sirtuin3deficiencyaccelerateshypertensivecardiacremodelingbyimpairingangiogenesis AT gaojianhuang sirtuin3deficiencyaccelerateshypertensivecardiacremodelingbyimpairingangiogenesis AT jinggao sirtuin3deficiencyaccelerateshypertensivecardiacremodelingbyimpairingangiogenesis AT chenglinhuang sirtuin3deficiencyaccelerateshypertensivecardiacremodelingbyimpairingangiogenesis AT mengweisun sirtuin3deficiencyaccelerateshypertensivecardiacremodelingbyimpairingangiogenesis AT jianwu sirtuin3deficiencyaccelerateshypertensivecardiacremodelingbyimpairingangiogenesis AT juanbu sirtuin3deficiencyaccelerateshypertensivecardiacremodelingbyimpairingangiogenesis AT weilishen sirtuin3deficiencyaccelerateshypertensivecardiacremodelingbyimpairingangiogenesis |