ISSN 2996-8215
International Journal of Cardiology | Vol. 12, No. 2, February 2021 | pp. 9–16
DOI: 10.46882/2021/IJC/000143
Original Research Article
Cardioprotective Effects of Canagliflozin in a Rat Model of Diabetic Cardiomyopathy via Mitofusin-2 Pathway Up-Regulation
Kenji Tanaka¹, Satoshi Yamada¹, Takashi Sato²
¹Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
²Division of Metabolic Diseases, Tokyo Medical and Dental University, Tokyo, Japan
Abstract:
Diabetic cardiomyopathy leads to progressive diastolic failure and myocardial structural derangement. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce heart failure event rates, but their direct impact on cardiomyocyte mitochondrial dynamics remains characterized. This study investigated the protective effects of canagliflozin on myocardial remodeling and mitochondrial structural integrity in a rat model of type 2 diabetes. Type 2 diabetes was induced in adult male Wistar rats via a high-fat diet combined with a low-dose streptozotocin injection. Diabetic rats were randomized to receive either canagliflozin (10 mg/kg/day, n = 15) or vehicle control (n = 15) via oral gavage for 8 weeks. Cardiac function was monitored using tissue Doppler echocardiography, and structural mitochondrial alignment was assessed via transmission electron microscopy. Canagliflozin significantly improved the diastolic mitral inflow E/A ratio compared to the vehicle group (1.45 ± 0.12 vs. 1.05 ± 0.08, p < 0.01). Electron microscopy revealed that canagliflozin treatment prevented mitochondrial fragmentation, preserving mitochondrial aspect ratios (2.42 ± 0.15 vs. 1.54 ± 0.11, p < 0.01). Western blot analysis demonstrated that canagliflozin up-regulated the expression of mitofusin-2 (Mfn2) and down-regulated dynamin-related protein 1 (Drp1), suppressing pro-apoptotic pathways. Canagliflozin significantly improves diastolic performance and mitigates diabetic cardiomyopathy in rats by preserving mitochondrial fusion structural pathways and optimizing metabolic morphology.
Keywords: Diabetic cardiomyopathy, Canagliflozin, SGLT2 inhibitors, Mitochondrial dynamics, Mitofusin-2, Diastolic function
Received: November 05, 2020; Revised: December 18, 2020; Accepted: January 10, 2021; Published: February 20, 2021