Dapagliflozin Attenuates Cardiac Remodeling in Mice Model of Cardiac Pressure Overload

被引:70
作者
Shi, Lin [1 ]
Zhu, Diqi [1 ]
Wang, Shoubao [1 ]
Jiang, Aixia [1 ]
Li, Fen [1 ,2 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Cardiol, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Shanghai Pediat Congenital Heart Dis Inst, Shanghai, Peoples R China
基金
美国国家科学基金会;
关键词
apoptosis; cardiac remodeling; dapagliflozin; FoxO1; hypertrophy; MAPKs; myocardial fibrosis; TAC; HEART-FAILURE; CARDIOVASCULAR OUTCOMES; NA+/H+-EXCHANGER; BLOOD-PRESSURE; HYPERTROPHY; INHIBITOR; APOPTOSIS; KINASE; EMPAGLIFLOZIN; PROTECTS;
D O I
10.1093/ajh/hpz016
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
BACKGROUND Dapagliflozin (DAPA) is an inhibitor of sodium-glucose cotransporter 2 prescribed for type 2 diabetes mellitus. DAPA plays a protective role against cardiovascular diseases. Nevertheless, the effect and mechanism of DAPA on pressure-overload-induced cardiac remodeling has not been determined. METHODS We used a transverse aortic constriction (TAC) induced cardiac remodeling model to evaluate the effect of DAPA. Twenty-four C57BL/6J mice were divided into 3 groups: Sham, TAC, and TAC + DAPA groups (n = 8, each). DAPA was administered by gavage (1.0 mg/kg/day) for 4 weeks in the TAC + DAPA group, and then the myocardial hypertrophy, cardiac systolic function, myocardial fibrosis, and cardiomyocyte apoptosis were evaluated. RESULTS Mice in TAC group showed increased heart weight/body weight, left ventricular (LV) diameter, LV posterior wall thickness, and decreased LV ejection fraction and LV fractional shortening. The collagen volume fraction and perivascular collagen area/luminal area ratio were significantly greater in the TAC group; the TUNEL-positive cell number and PARP level were also increased. We found that DAPA treatment reduced myocardial hypertrophy, myocardial interstitial and perivascular fibrosis, and cardiomyocyte apoptosis. Furthermore, DAPA administration inhibited phosphorylation of P38 and JNK in TAC group. In addition, the inhibited phosphorylation of FoxO1 in the TAC mice was upregulated by DAPA administration. CONCLUSION DAPA administration had a cardioprotective effect by improving cardiac systolic function, inhibiting myocardial fibrosis and cardiomyocyte apoptosis in a TAC mouse model, indicating that it could serve as a new therapy to prevent pathological cardiac remodeling in nondiabetics.
引用
收藏
页码:452 / 459
页数:8
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