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Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis

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...

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Autores principales: Forouzandeh, Farshad, Salazar, Gloria, Patrushev, Nikolay, Xiong, Shiqin, Hilenski, Lula, Fei, Baowei, Alexander, R. Wayne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338706/
https://www.ncbi.nlm.nih.gov/pubmed/25527624
http://dx.doi.org/10.1161/JAHA.114.001202
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author Forouzandeh, Farshad
Salazar, Gloria
Patrushev, Nikolay
Xiong, Shiqin
Hilenski, Lula
Fei, Baowei
Alexander, R. Wayne
author_facet Forouzandeh, Farshad
Salazar, Gloria
Patrushev, Nikolay
Xiong, Shiqin
Hilenski, Lula
Fei, Baowei
Alexander, R. Wayne
author_sort Forouzandeh, Farshad
collection PubMed
description 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.
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spelling pubmed-43387062015-02-27 Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis Forouzandeh, Farshad Salazar, Gloria Patrushev, Nikolay Xiong, Shiqin Hilenski, Lula Fei, Baowei Alexander, R. Wayne J Am Heart Assoc Original Research 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. Blackwell Publishing Ltd 2014-12-19 /pmc/articles/PMC4338706/ /pubmed/25527624 http://dx.doi.org/10.1161/JAHA.114.001202 Text en © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Forouzandeh, Farshad
Salazar, Gloria
Patrushev, Nikolay
Xiong, Shiqin
Hilenski, Lula
Fei, Baowei
Alexander, R. Wayne
Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis
title Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis
title_full Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis
title_fullStr Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis
title_full_unstemmed Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis
title_short Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis
title_sort metformin beyond diabetes: pleiotropic benefits of metformin in attenuation of atherosclerosis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338706/
https://www.ncbi.nlm.nih.gov/pubmed/25527624
http://dx.doi.org/10.1161/JAHA.114.001202
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