Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet

Abstract Statins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were d...

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Autores principales:	Fei Luo, Yuan Guo, Gui-yun Ruan, Jun-ke Long, Xi-long Zheng, Qin Xia, Shui-ping Zhao, Dao-quan Peng, Zhen-fei Fang, Xiang-ping Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8d81b5b44b27464da383e7ac6695964e
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spelling	oai:doaj.org-article:8d81b5b44b27464da383e7ac6695964e2021-12-02T16:06:01ZCombined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet10.1038/s41598-017-02080-w2045-2322https://doaj.org/article/8d81b5b44b27464da383e7ac6695964e2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02080-whttps://doaj.org/toc/2045-2322Abstract Statins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were designed to evaluate whether combined use of metformin and atorvastatin can achieve additional benefits. In rabbits fed a high-cholesterol diet, we evaluated the effects of the combination therapy on atherosclerotic plaques, lipid profiles, blood glucose levels, liver and kidney functions. Effects of combination therapy on cholesterol efflux and the expression of related transporters were studied in vitro. Our results showed that the combination therapy induced a more significant decrease in atherosclerotic lesion area than atorvastatin without additional lipid-lowering effect. The combination therapy significantly increased the percentage of large high-density lipoprotein subfraction. The intravenous glucose tolerance test showed that atorvastatin-treated rabbits had an increased area under the curve for time-dependent glucose levels after a bolus injection of glucose, which was completely reversed by metformin treatment. In cultured macrophages, co-treatment with metformin and atorvastatin promoted cholesterol efflux and up-regulated expression of ATP-binding cassette transporters A1 and G1. Taken together, our results suggest that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages.Fei LuoYuan GuoGui-yun RuanJun-ke LongXi-long ZhengQin XiaShui-ping ZhaoDao-quan PengZhen-fei FangXiang-ping LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fei Luo Yuan Guo Gui-yun Ruan Jun-ke Long Xi-long Zheng Qin Xia Shui-ping Zhao Dao-quan Peng Zhen-fei Fang Xiang-ping Li Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet
description	Abstract Statins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were designed to evaluate whether combined use of metformin and atorvastatin can achieve additional benefits. In rabbits fed a high-cholesterol diet, we evaluated the effects of the combination therapy on atherosclerotic plaques, lipid profiles, blood glucose levels, liver and kidney functions. Effects of combination therapy on cholesterol efflux and the expression of related transporters were studied in vitro. Our results showed that the combination therapy induced a more significant decrease in atherosclerotic lesion area than atorvastatin without additional lipid-lowering effect. The combination therapy significantly increased the percentage of large high-density lipoprotein subfraction. The intravenous glucose tolerance test showed that atorvastatin-treated rabbits had an increased area under the curve for time-dependent glucose levels after a bolus injection of glucose, which was completely reversed by metformin treatment. In cultured macrophages, co-treatment with metformin and atorvastatin promoted cholesterol efflux and up-regulated expression of ATP-binding cassette transporters A1 and G1. Taken together, our results suggest that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages.
format	article
author	Fei Luo Yuan Guo Gui-yun Ruan Jun-ke Long Xi-long Zheng Qin Xia Shui-ping Zhao Dao-quan Peng Zhen-fei Fang Xiang-ping Li
author_facet	Fei Luo Yuan Guo Gui-yun Ruan Jun-ke Long Xi-long Zheng Qin Xia Shui-ping Zhao Dao-quan Peng Zhen-fei Fang Xiang-ping Li
author_sort	Fei Luo
title	Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet
title_short	Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet
title_full	Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet
title_fullStr	Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet
title_full_unstemmed	Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet
title_sort	combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8d81b5b44b27464da383e7ac6695964e
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Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet

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