Several 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. ApoE-/- 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. Empagliflozin 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. The early atherosclerotic lesion size was less visible in empagliflozin-treated mice. Empagliflozin could decrease lipid profiles and sympathetic activity in atherosclerosis.

中文翻译：

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Empagliflozin 通过调节脂质谱和交感神经活动防止动脉粥样硬化进展

几项大型临床试验证实了钠-葡萄糖协同转运蛋白 2 抑制剂 (SGLT2i) 对 2 型糖尿病患者的心脏保护作用。然而，恩格列净作为 SGLT2i 是否可以缓解非糖尿病状态下的动脉粥样硬化进展仍然未知。ApoE-/- 小鼠用西方饮食喂养 12 周以诱导动脉粥样硬化。在第 7 周，一组小鼠接受含有 empagliflozin（10 mg/kg/天）的饮用水，而另一组则给予正常水。在第 12 周时，收获各组的全主动脉。对动脉粥样硬化病变区域和大小进行油红 O、HE 和 Movat 染色。小鼠血清脂质谱（总胆固醇 [TC]、甘油三酯 [TG]、低密度脂蛋白-c [LDL] 和高密度脂蛋白-c [HDL]）、全身炎症水平（IL-1β、IL-6和IL-10)、肾素-血管紧张素-醛固酮系统(RAAS)成分和交感神经活性(去甲肾上腺素和神经肽Y)指标通过ELISA测定。Empagliflozin 减少了 ApoE-/- 小鼠主动脉根部的动脉粥样硬化病变负担（-8.6%，P = 0.004）。此外，恩格列净还能降低体重（-3.27 g，P = 0.002）、血脂（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（肾素 [-9.3 ng/L，P = 0.047]；醛固酮 [-16.7 ng/L，P < 0.001]）和交感神经活性（去甲肾上腺素 [-8.9 ng] /L，P = 0.019]；神经肽 Y [-8.8 ng/L，P = 0.002])。然而，恩格列净的抗炎作用并不明显。在恩格列净治疗的小鼠中，早期动脉粥样硬化病变的大小不太明显。