TY - JOUR
T1 - Metformin beyond diabetes
T2 - Pleiotropic benefits of metformin in attenuation of atherosclerosis
AU - Forouzandeh, Farshad
AU - Salazar, Gloria
AU - Patrushev, Nikolay
AU - Xiong, Shiqin
AU - Hilenski, Lula
AU - Fei, Baowei
AU - Wayne Alexander, R.
N1 - Publisher Copyright:
© 2014 The Authors.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Aging
KW - Angiotensin
KW - Atherosclerosis
KW - Metformin
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U2 - 10.1161/JAHA.114.001202
DO - 10.1161/JAHA.114.001202
M3 - Article
C2 - 25527624
AN - SCOPUS:84937768865
SN - 2047-9980
VL - 3
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 6
M1 - 001202
ER -