Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury

• Published in: Journal of endocrinology Vol. 236; no. 2; pp. 69 - 84
• Main Authors: Tanajak, Pongpan, Sa-nguanmoo, Piangkwan, Sivasinprasasn, Sivaporn, Thummasorn, Savitree, Siri-Angkul, Natthaphat, Chattipakorn, Siriporn C, Chattipakorn, Nipon
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.02.2018; Portland Press Ltd The Biochemical Society
• Subjects: Animals; Antidiabetics; Benzhydryl Compounds - pharmacology; Benzhydryl Compounds - therapeutic use; Blood pressure; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Caspase; Caspase-3; Cytoprotection - drug effects; Diet, High-Fat; Dipeptidyl-peptidase IV; Glucosides - pharmacology; Glucosides - therapeutic use; Heart; Heart - drug effects; Heart diseases; High fat diet; Insulin; Ischemia; Male; Metabolic disorders; Mitochondria; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - pathology; Occlusion; Peptidase; Rats; Rats, Wistar; Reperfusion; Rodents; Sodium; Sodium-glucose cotransporter; Ventricle; Ventricular Dysfunction, Left - prevention & control; Ventricular Function, Left - drug effects; Vildagliptin - pharmacology; Vildagliptin - therapeutic use; pre-diabetes; DPP4 inhibitors; vildagliptin; dapagliflozin; cardioprotection; cardiac I/R injury; SGLT2 inhibitors
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1530/JOE-17-0457

Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese insulin-resistant rats with/without cardiac I/R injury. The high-fat (HF) diet-induced obese insulin-resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa) and combination drugs (HFDaVil). At the end, I/R injury was induced by a 30-min left anterior descending coronary occlusion and 120-min reperfusion. Dapagliflozin showed a greater efficacy than vildagliptin in improving the metabolic impairments, low frequency/high frequency (LF/HF) ratio, systolic blood pressure and left ventricular (LV) function in comparison to HFV rats. In cardiac I/R injury, dapagliflozin had a greater efficacy than vildagiptin in decreasing mitochondrial DRP1, cleaved caspase 3, LV dysfunction and infarct size in comparison to HFV rats. However, the combined therapy showed the greatest efficacy in attenuating LV dysfunction, mitochondrial DRP1 and infarct size in comparison to HFV rats. In conclusion, dapagliflozin has a more pronounced effect than vildagliptin in obese insulin-resistant rats for the improvement of LV function. In rats with cardiac I/R injury, although dapagliflozin had a greater efficacy on cardioprotection than vildagliptin, the combined therapy exerted the highest cardioprotective effects potentially by reducing mitochondrial fission.