Dapagliflozin (1.0 mg/kg/day) reduced myocardial hypertrophy, fibrosis, and cardiomyocyte apoptosis while improving systolic function in a mouse model of cardiac pressure overload.
Does dapagliflozin attenuate cardiac remodeling in a mouse model of cardiac pressure overload?
Dapagliflozin attenuates pressure-overload-induced cardiac remodeling, fibrosis, and apoptosis in a non-diabetic mouse model, providing mechanistic insight into its cardioprotective effects.
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.
Shi et al. (Fri,) conducted a other in Cardiac pressure overload and cardiac remodeling (n=24). Dapagliflozin vs. Sham and TAC (no dapagliflozin) was evaluated on Myocardial hypertrophy, cardiac systolic function, myocardial fibrosis, and cardiomyocyte apoptosis. Dapagliflozin (1.0 mg/kg/day) reduced myocardial hypertrophy, fibrosis, and cardiomyocyte apoptosis while improving systolic function in a mouse model of cardiac pressure overload.