Empagliflozin Exert An Antiatherogenic Effect By Inhibiting Macrophage Foamy

Background:Atherosclerotic cardiovascular disease currently remains the leading cause of death in most parts of the world.But the treatment for the disease still has many limitations.In recent years,some authoritative clinical studies have found that Englegrazin reduces the risk of cardiovascular events in diabetic patients,which may imply that SGLT2 inhibitor can play a role beyond lowering blood glucose.Objective:In this study,we attempted to explore the effect of SGLT2 inhibitor（empagliflozin）on vascular atherosclerosis after removing the effect of diabetes.Methods:In an in vivo experiment,30 Apo E-/-mice were fed with high-fat diet for8 weeks to induce the formation of atheroscloma lesions,and then empagliflozin was administered intragastric.The treatment group was divided into low dose group and high dose group.Ten C57BL/6J mice were used as the control group.The control group was fed with normal diet and gavaged the same amount of normal saline during the treatment.After 8 weeks of treatment,the aorta tree and aortic valve area were stained with oil red,and the infiltration of IL-6,IL-1β and NF-κB in the diseased tissue was evaluated by immunohistochemistry on the cross section of blood vessels.Meanwhile,serum was collected to detect the levels of inflammatory factors.In an in vitro experiment,the RAW264.7 cell line was selected and ox-LDL was used to induce the release of proinflammatory factors,and different doses of empagliflozin were added.The phagocytosis of macrophages to oxidized LOW density lipoprotein,and the expression of inflammatory factors at the protein and RNA levels were measured.Results:Empagliflozin reduced the area of atherosclerotic plaque and macrophage infiltration in atherosclerotic plaques,decreased the expression of NF-κB and inflammatory factors in local plaque tissues of APOE-/-mice fed with high-fat diet.In vitro results showed that Empagliflozin can improve the protein expression level of p-AMPK affected by ox-LDL and reduce the gene expression level of inflammatory factors,thus playing an anti-atherosclerosis role.Conclusion:Empagliflozin,an inhibitor of SGLT-2,may improve energy metabolism and reduce the expression of inflammatory factors by activating AMPK,thereby improving atherosclerosis,which has positive significance for the treatment of atherosclerotic diseases.