The sirtuin 6 prevents angiotensin II-mediated myocardial fibrosis and injury by targeting AMPK-ACE2 signaling
文献类型：期刊论文
| 作者 | Zhang, Zhen-Zhou2,3; Cheng, Yu-Wen2; Jin, Hai-Yan2; Chang, Qing2; Xu, Ying-Le2; Xu, Ran2; Song, Bei2; Zhong, Jiu-Chang2,3; Jin, Hai-Yan4; Shang, Qian-Hui1,5 |
| 刊名 | ONCOTARGET
 |
| 出版日期 | 2017 |
| 卷号 | 8期号:42页码:72302-72314 |
| 关键词 | SIRT6 angiotensin-converting enzyme 2 connective tissue growth factor fibrosis myocardial injury |
| ISSN号 | 1949-2553 |
| DOI | 10.18632/oncotarget.20305 |
| 文献子类 | Article |
| 英文摘要 | Sirtuin 6 (SIRT6) is an important modulator of cardiovascular functions in health and diseases. However, the exact role of SIRT6 in heart disease is poorly defined. We hypothesized that SIRT6 is a negative regulator of angiotensin II (Ang II)mediated myocardial remodeling, fibrosis and injury. The male Sprague-Dawley rats were randomized to Ang II ( 200 ng/kg/min) infusion with an osmotic minipump and pretreated with recombinant plasmids adeno-associated viral vector (AAV)-SIRT6 (pAAV-SIRT6) or pAAV-GFP for 4 weeks. Ang II triggered downregulated levels of SIRT6 and angiotensin-converting enzyme 2 (ACE2) and upregulated expression of connective tissue growth factor (CTGF) and proinflammatory chemokine fractalkine (FKN), contributing to enhanced cardiac fibrosis and ultrastructural injury. Reduced levels of phosphorylated pAMPK-a, increased myocardial hypertrophy and impaired heart dysfunction were observed in both Ang II-induced hypertensive rats and ACE2 knockout rats, characterized with increases in heart weight and left ventricular (LV) posterior wall thickness and decreases in LV ejection fraction and LV fractional shortening. More importantly, pAAV-SIRT6 treatment strikingly potentiated cardiac levels of pAMPKa and ACE2 as well as decreased levels of CTGF, FKN, TGF beta 1, collagen I and collagen III, resulting in alleviation of Ang II-induced pathological hypertrophy, myocardial fibrosis, cardiac dysfunction and ultrastructural injury in hypertensive rats. In conclusion, our findings confirmed cardioprotective effects of SIRT6 on pathological remodeling, fibrosis and myocardial injury through activation of AMPK-ACE2 signaling and suppression of CTGF-FKN pathway, indicating that SIRT6 functions as a partial agonist of ACE2 and targeting SIRT6 has potential therapeutic importance for cardiac fibrosis and heart disease. |
| 学科主题 | Oncology ; Cell Biology |
| WOS关键词 | CONVERTING ENZYME 2 ; HEART-FAILURE ; PROTECTS CARDIOMYOCYTES ; CARDIAC-HYPERTROPHY ; C-JUN ; ACTIVATION ; MICE ; FRACTALKINE ; STRESS ; CELLS |
| 语种 | 英语 |
| WOS记录号 | WOS:000411509400076 |
| 出版者 | IMPACT JOURNALS LLC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1111]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Zunyi Med Coll, Affiliated Hosp, Inst Clin Med Res, Zunyi 563003, Peoples R China; 2.Shanghai Jiao Tong Univ, Shanghai Inst Hypertens, Shanghai Key Lab Hypertens, State Key Lab Med Genom,Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai 200025, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Mental Hlth, Shanghai 200025, Peoples R China; 5.Zunyi Med Coll, Affiliated Hosp, Dept Cardiol, Zunyi 563003, Peoples R China; 6.Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Zhang, Zhen-Zhou,Cheng, Yu-Wen,Jin, Hai-Yan,et al. The sirtuin 6 prevents angiotensin II-mediated myocardial fibrosis and injury by targeting AMPK-ACE2 signaling[J]. ONCOTARGET,2017,8(42):72302-72314. |
| APA | Zhang, Zhen-Zhou.,Cheng, Yu-Wen.,Jin, Hai-Yan.,Chang, Qing.,Xu, Ying-Le.,...&,.(2017).The sirtuin 6 prevents angiotensin II-mediated myocardial fibrosis and injury by targeting AMPK-ACE2 signaling.ONCOTARGET,8(42),72302-72314. |
| MLA | Zhang, Zhen-Zhou,et al."The sirtuin 6 prevents angiotensin II-mediated myocardial fibrosis and injury by targeting AMPK-ACE2 signaling".ONCOTARGET 8.42(2017):72302-72314. |
入库方式： OAI收割
来源：上海营养与健康研究所
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