Activation of Silent Information Regulator 6 Signaling Attenuates Myocardial Fibrosis by Reducing TGFb1-Smad2/3 Signaling in a Type 2 Diabetic Animal Model  

作　　者：Liming Yu Jian Wang Xue Dong Yue Hu Linyu Luo Xiaodong Xue Yang Wang 

机构地区：[1]Department of Cardiovascular Surgery,General Hospital of Northern Theater Command,Shenyang,Liaoning 110016,China [2]Department of Ultrasound,Chinese People’s Liberation Army 985 Hospital,Taiyuan,Shanxi 030001,China [3]Outpatient Department of Liaoning Military Region,General Hospital of Northern Theater Command,Shenyang,Liaoning 110032,China.

出　　处：《Cardiology Discovery》2022年第1期6-12,共7页心血管病探索（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(81700264);Postdoctoral Science Foundation Grant of China(2018M643839);the Natural Science Foundation of Liaoning Province(2020-MS-036).

摘　　要：Objective:Long-term diabetes can result in ventricular hypertrophic remodeling,tissue fibrosis,myocardial metabolic defection,and eventually,heart failure.Silent information regulator 6(SIRT6)exerts beneficial effects against cardiovascular diseases.This study is aimed to investigate whether the direct regulation of myocardial SIRT6 signaling affects cardiac performance in the case of diabetes.Meanwhile,we sought to explore the underlying mechanisms.Methods:Sprague Dawley(SD)rats were used in this experiment.Briefly,type 2 diabetic animal model was generated by streptozotocin administration along with feeding a high-fat diet.The SD rats were randomly assigned to non-diabetic group,diabetic group,diabetic injected with empty adenoviral vectors group and diabetic injected with adenoviral vectors expressing SIRT6 group(n=10,respectively).The animals were kept for another 4 weeks before sacrifice.Cardiac performance was evaluated by echocardiography.Myocardial fibrosis was determined by Masson’s trichrome staining.Myocardial SIRT6 signaling and fibrosis related molecules were measured by western blotting.Results:The diabetic myocardium exhibited markedly enhanced TGFb1-Smad2/3-induced myocardial fibrosis and reduced SIRT6 and AMP-activated protein kinase(AMPK)signaling.After 4 weeks of SIRT6 adenoviral vector infection,myocardial tissues exhibited markedly enhanced SIRT6 and AMPK signaling.Additionally,myocardial fibrosis and TGFb1-Smad2/3 signaling were both attenuated in the diabetic injected with adenoviral vectors expressing SIRT6 group.Conclusions:SIRT6-AMPK signaling suppressed the progression of tissue fibrosis in diabetes mellitus rats by inhibiting TGFb1 and its downstream effector Smad2/3.SIRT6 might serve as an alternative therapeutic target for diabetes-related cardiovascular diseases.

关 键 词：AMP-activated protein kinase DIABETES FIBROSIS Silent information regulator 6 

分 类 号：R58[医药卫生—内分泌]