Abstract
BackgroundSeveral large clinical trials have confirmed the cardioprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes. However, whether empagliflozin, as an SGLT2i, could alleviate atherosclerosis progression in non-diabetic states remain unknown.MethodsApoE-/- mice were fed a Western diet for 12 weeks to induce atherosclerosis. On the 7th week, a group of mice were treated with drinking water containing empagliflozin (10 mg/kg/day), while another group was given normal water. At the 12th week, the whole aortas of each group were harvested. Oil Red O, HE and Movat staining were performed for atherosclerotic lesion area and size. Mouse serum lipid profiles (total cholesterol [TC], triglyceride [TG], low-density lipoprotein-c [LDL], and high-density lipoprotein-c [HDL]), systemic inflammation levels (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) components and sympathetic activity (norepinephrine and neuropeptide Y) indicators were measured by ELISA.ResultsEmpagliflozin reduced the atherosclerotic lesion burden (-8.6 %, P = 0.004) at aortic root in ApoE-/- mice. In addition, empagliflozin decreased body weight (-3.27 g, P = 0.002), lipid profiles (TC: [-15.3 mmol/L, P = 0.011]; TG: [-2.4 mmol/L, P < 0.001]; LDL: [-2.9 mmol/L, P = 0.010]), RAAS (renin [-9.3 ng/L, P = 0.047]; aldosterone [-16.7 ng/L, P < 0.001]) and sympathetic activity (norepinephrine [-8.9 ng/L, P = 0.019]; neuropeptide Y [-8.8 ng/L, P = 0.002]). However, the anti-inflammatory effect of empagliflozin was not significantly evident.ConclusionsThe early atherosclerotic lesion size was less visible in empagliflozin-treated mice. Empagliflozin could decrease lipid profiles and sympathetic activity in atherosclerosis.
Highlights
Several large clinical trials have confirmed the cardioprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes
The EMPA group is fed on a Western diet and received drinking water containing 10 mg/kg/d [23,24,25] of empagliflozin (CAS Nanjing Drum Tower Hospital (No).: 864070-44-0, MedChemExpress, NJ, USA) beginning at the 7th week
The SGLT2i attenuates atherosclerotic lesion area To assess the therapeutic role of SGLT2i in atherosclerosis in mice, ApoE-/- mice were fed a Western diet for 12 weeks (AS group), while the EMPA group received empagliflozin at a dose of 10 mg/kg/day from the 7th to the 12th week
Summary
Several large clinical trials have confirmed the cardioprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes. SGLT2 inhibitors (SGLT2i) can reduce glucose reabsorption in the proximal tubules and increase urine. Recent clinical studies have shown that SGLT2i can reduce cardiovascular mortality and heart failure hospitalization rates in patients with type 2 diabetes [4,5,6], making them the first hypoglycemic agents to reduce cardiovascular adverse events independent of glycemic control [7]. SGLT2i can inhibit inflammation and improve insulin resistance[8], as well as modulate the gut microbiota of type 2 diabetes mice[9]. Some studies reported that their cardioprotective role could be associated with reduced arterial stiffness [11], improved myocardial metabolism [12] and increased antioxidative capacity [13]. Ken et al systematically reviewed preclinical data on the cardioprotective effects of SGLT2i and found that a reduction in atherosclerosis was one of the underlying mechanisms [14]
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