title: The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE-/-mice fed a western diet.
abstract: A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action.
  
  
  
  Forty-eight 5-week-old male ApoE-/-mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0.1 mg/kg, empagliflozin 1 mg/kg and empagliflozin 3 mg/kg (n = 12/group). Plaque size and composition in the aortic arch/valve areas and cardiovascular risk variables in the blood and tissues were evaluated. Insulin resistance was estimated by HOMA and adiponectin levels. Body composition was determined using dual-energy x-ray absorptiometry.
  
  
  
  After 8 weeks of treatment, the empagliflozin and glimepiride groups exhibited decreased blood glucose levels. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the empagliflozin groups than in the control or glimepiride groups. Insulin resistance and circulating concentrations of TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A and urinary microalbumin decreased after empagliflozin treatment, and this significantly correlated with plaque size. Empagliflozin treatment reduced weight and fat mass, lipid droplets in the liver, fat cell size, mRNA expression of Tnf, Il6 and Mcp-1 (also known as Ccl2) and the infiltration of inflammatory cells in plaque and adipose tissue compared with the control or glimepiride group. Empagliflozin treatment increased adiponectin levels.
  
  
  
  Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by empagliflozin.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070.
authors.forename: Tae Jung
authors.initials: TJ
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070.
authors.forename: Ghayoung
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Maeng
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070.
authors.forename: Dong Hwa
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070.
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070.
authors.forename: Hak Chul
authors.initials: HC
authors.lastname: Jang
authors.affiliation: Department of Pathology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Young-Bum
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-city, South Korea, 463-070. limsoo@snu.ac.kr.
authors.forename: Soo
authors.initials: S
authors.lastname: Lim
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D015153:Blotting, Western; D039521:CD11c Antigen / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D066273:Diet, Western / Q000009:adverse effects*; D005960:Glucosides / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; D001559:Benzhydryl Compounds; D039521:CD11c Antigen; D005960:Glucosides; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C570240:empagliflozin
keywords: Atherosclerosis; Insulin resistance; Sodium glucose cotransporter; Type 2 diabetes