title: Metformin beyond diabetes: pleiotropic benefits of metformin in attenuation of atherosclerosis.
abstract: BACKGROUND
  Clinical studies show that metformin attenuates all‐cause mortality and myocardial infarction compared with other medications for type 2 diabetes, even at similar glycemic levels. However, there is paucity of data in the euglycemic state on the vasculoprotective effects of metformin. The objectives of this study are to evaluate the effects of metformin on ameliorating atherosclerosis.
  
  
  RESULTS
  Using ApoE−/− C57BL/6J mice, we found that metformin attenuates atherosclerosis and vascular senescence in mice fed a high‐fat diet and prevents the upregulation of angiotensin II type 1 receptor by a high‐fat diet in the aortas of mice. Thus, considering the known deleterious effects of angiotensin II mediated by angiotensin II type 1 receptor, the vascular benefits of metformin may be mediated, at least in part, by angiotensin II type 1 receptor downregulation. Moreover, we found that metformin can cause weight loss without hypoglycemia. We also found that metformin increases the antioxidant superoxide dismutase‐1.
  
  
  CONCLUSIONS
  Pleiotropic effects of metformin ameliorate atherosclerosis and vascular senescence.
authors.affiliation: Division of Cardiology, Emory University School of Medicine, Atlanta, GA
authors.forename: Farshad
authors.initials: F
authors.lastname: Forouzandeh
authors.forename: Gloria
authors.initials: G
authors.lastname: Salazar
authors.forename: Nikolay
authors.initials: N
authors.lastname: Patrushev
authors.forename: Shiqin
authors.initials: S
authors.lastname: Xiong
authors.forename: Lula
authors.initials: L
authors.lastname: Hilenski
authors.forename: Baowei
authors.initials: B
authors.lastname: Fei
authors.forename: R Wayne
authors.initials: RW
authors.lastname: Alexander
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology*; D016922:Cellular Senescence / Q000187:drug effects; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D002317:Cardiovascular Agents; D007004:Hypoglycemic Agents; D044140:Receptor, Angiotensin, Type 1; D008687:Metformin; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1