Metformin beyond diabetes: Pleiotropic benefits of metformin in attenuation of atherosclerosis

Farshad Forouzandeh, Gloria Salazar, Nikolay Patrushev, Shiqin Xiong, Lula Hilenski, Baowei Fei, R. Wayne Alexander

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


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. Methods and 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. Conclusion-Pleiotropic effects of metformin ameliorate atherosclerosis and vascular senescence.

Original languageEnglish (US)
Article number001202
JournalJournal of the American Heart Association
Issue number6
StatePublished - 2014
Externally publishedYes


  • Aging
  • Angiotensin
  • Atherosclerosis
  • Metformin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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