Table 2 Summary of the effects of SGLT-2 inhibitors on cardiac structure in animal models
Animal species | Model | Drug/dose/route | Major findings | Interpretation | References |
|---|---|---|---|---|---|
Wistar rats | Streptozotocin-induced diabetic cardiomyopathy | Empagliflozin (30 or 10 mg/kg/days)/PO/8 weeks | ↓ Disorganized cell arrays and focal necrosis in dose-dependent manner | Empagliflozin improved structural changes in the myocardium of streptozotocin-induced diabetic cardiomyopathy rats | [62] |
SHR/NDmcr-cp(+/+) rats | Prediabetes/metabolic syndrome | 0.03% empagliflozin/diet/10 weeks | ↓ LV weight and cardiomyocyte size ↓ Interstitial fibrosis | Empagliflozin improved cardiac hypertrophy and interstitial fibrosis in genetic prediabetic metabolic syndrome rats | [57] |
db/db mice | Diabetes/obesity (diastolic dysfunction and LVH) | Empagliflozin (10 mg/kg/days)/PO/5 weeks | ↓ Cardiomyocyte cross sectional area ↓ Interstitial collagen I and III depositions ↓ SGK1 and ENaC expressions | Empagliflozin improved LVH and myocardial fibrosis in db/db mice | [59] |
db/db mice | Diabetes/obesity (diastolic dysfunction and LVH) | 0.03% empagliflozin/diet/10 weeks | ↓ Cardiac interstitial and pericoronary arterial fibrosis ↓ Coronary arterial thickening | Empagliflozin attenuated cardiovascular remodeling in db/db mice | [58] |
ob/ob mice | T2DM/obesity (LV diastolic dysfunctions) | Empagliflozin (10 mg/kg/days)/PO/6 weeks | ↔ LV mass, myocardial fibrosis ↓ Anf, β-Mhc mRNA levels ↓ p-ERKs, p-JNKs and p-P38 expressions | Empagliflozin attenuated markers of cardiac hypertrophy and remodeling, but not altered cardiac fibrosis in ob/ob mice | [60] |
BTBR ob/ob mice | T2DM | Dapagliflozin (1 mg/kg/days)/PO/8 weeks | ↓ Collagen-1 and collagen-3 mRNA levels ↓ % fibrosis | Dapagliflozin attenuated cardiac fibrosis in BTBR ob/ob mice | [63] |
Rats | High fat diet induced obese-insulin resistance for 4 weeks then I/R injury by LAD ligation | Dapagliflozin (1 mg/kg/days)/PO/4 weeks | ↓ Infarct size | Dapagliflozin attenuated MI size in pre-diabetic rats with cardiac I/R injury | [64] |
Wistar rats | MI by LAD ligation in rats | Dapagliflozin (0.1 mg/kg/days)/PO/Start after 1-day infarction for 4 weeks | ↔ Infarct size ↓ Myofibroblast infiltration and cardiac fibrosis | Dapagliflozin attenuated myofibroblast infiltration during post-infarction remodeling in rats | [65] |
cmlc2::GFP zebrafish embryos | Aristolochic acid induced heart failure | Empagliflozin (0.1, 10 μM)/media/3 days | ↓ Morphologic changes in a concentration-dependent manner included unlooping defects, cardiac edema, and deformed cardiac chambers ↓ ANP, BNP signaling | Empagliflozin improved heart failure morphology and attenuated heart failure markers in zebrafish embryos | [66] |