Empagliflozin protects against atherosclerosis progression by modulating lipid profiles and sympathetic activity

Background 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. Methods 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. Results 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. Conclusions The early atherosclerotic lesion size was less visible in empagliflozin-treated mice. Empagliflozin could decrease lipid profiles and sympathetic activity in atherosclerosis.

CABG MODELS FLOW SIMULATION STUDY ON THE EFFECTS OF VALVE REMNANTS IN THE VENOUS GRAFT

Venous valves and sinuses are frequently observed in vein grafts in the coronary artery bypass grafts (CABG). However, from the biomedical engineering viewpoint, vein grafts are always assumed as smooth tubes in the existing simulations, and no effort has been made to investigate the effects of jaggedness of the graft inner wall due to the valve cusps remnants and valve sinus (in case of valve-stripped saphenous vein (SV) grafts) on the blood flow patterns and hemodynamic parameters (HPs). In this paper, the effects of the inner surface irregularities of a vein graft on the blood flow is investigated in the graft as well as in the distal anastomotic region, with a more realistic geometry of valve-stripped SV, by means of numerical simulation of pulsatile, Newtonian blood flow. The simulation results demonstrate that the valve remnants and sinuses cause disturbances in the flow field within the graft (due to vortices formation within the valve sinuses) and undesirable distribution of HPs, which can result in early atherosclerotic lesion development in the graft.