Potential cardioprotective effect of Vitamin D and sodium-glucose transport protein 2 inhibitor in improving cardiac hypertrophy and fibrosis in Type 2 diabetic rats

Background: Diabetes mellitus (DM) is a major risk factor for cardiovascular diseases. The progression of myocardial abnormalities due to DM occurs slowly but is progressive and asymptomatic. Sodium-glucose transport protein 2 inhibitors (SGLT-2i) and Vitamin D have potential cardioprotective properties that inhibit cardiomyocyte fibrosis and hypertrophy, which are early structural changes that occur in the heart of DM patients. Aim: The study aimed to determine the potential protective effects of SGLT-2i and Vitamin D administration on cardiac hypertrophy and fibrosis in Type 2 diabetic rats.Methods: This is an experimental study with a post-test-only control group design. Thirty-two male Wistar rats were given a high-fat/high-glucose (HF/HG) diet. After 3 weeks, rats were given an injection of streptozotocin (STZ 35 mg/kg) to induce pancreatic damage. The diabetic rats were then divided into four groups (n = 8 per group): untreated diabetic group (HF/HG/STZ), the diabetic group treated with empagliflozin (EMPA) 10 mg/kg body weight (BW) (HF/HG/ STZ+EMPA), the diabetic group treated with Vitamin D 225 IU/day (HF/HG/STZ+VitD), and the diabetic group treated with a combination of EMPA 10 mg/kg BW and Vitamin D 225 IU/day (HF/ HG/STZ+EMPA+VitD). Treatments were given by oral gavage for 8 weeks. Left ventricular biopsy was performed at week 13 to examine collagen deposition, the cardiomyocyte cross-sectional area (CSA), and the mRNA expression of β-myosin heavy chain (β-MHC) and transforming growth factor-β (TGF-β). All the obtained data were analyzed statistically. Results: The administration of EMPA, Vitamin D, and combination therapy of EMPA and Vitamin D reduced the mRNA expression of β-MHC and TGF-β in diabetic rats compared to the untreated diabetic group. The administration of EMPA, Vitamin D, and combination therapy also resulted in a decrease in both the cardiomyocyte CSA and collagen deposition. Compared to monotherapy, combination therapy led to significantly better parameter reduction. Conclusion: Administration of EMPA, Vitamin D, and combination therapy improved cardiac hypertrophy and fibrosis in type 2 diabetic rats.Relevance for Patients: The combination of Vitamin D and SGLT-2i may be proposed as a cardioprotective strategy and preventive measure to reduce the incidence of cardiovascular disease in patients with Type 2 DM.