Metformin ameliorates Ox-LDL-induced foam cell formation in raw264.7 cells by promoting ABCG-1 mediated cholesterol efflux

doi:10.1016/j.lfs.2018.09.024

科研成果详情

题名	Metformin ameliorates Ox-LDL-induced foam cell formation in raw264.7 cells by promoting ABCG-1 mediated cholesterol efflux
作者	He, Xuan 1; Chen, Xiufang2; Wang, Lei 1; Wang, Wenqing 1; Liang, Qiao 1; Yi, Long 1; Wang, Yong 1; Gao, Qian 1
发表日期	2019
发表期刊	LIFE SCIENCES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Diabetes Atherosclerosis Foam cell Cholesterol efflux ABCG-1
其他关键词	DENSITY-LIPOPROTEINS ; LIPID-ACCUMULATION ; GLUCOSE CONTROL ; MACROPHAGES ; ATHEROSCLEROSIS ; CD36 ; MECHANISMS ; EXPRESSION ; ABCA1 ; SUPPRESSES
摘要	Aims: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Cholesterol efflux of lipid-loaded macrophages mediated by ATP binding cassette (ABC) cholesterol transporters, on the other hand, has been shown to attenuate atherosclerosis progression in patients with unknown mechanism. We therefore sought to test the effect of metformin that reduced cardiovascular risk in diabetic patients independent of its hypoglycemia effect on cholesterol transport in murine raw264.7 macrophages. Materials and methods: Mouse raw264.7 macrophages were loaded with Ox-LDL (50 mu g/ml) for 24 h before incubated with metformin (15 mu M) for 24 h. Foam cell formation was assessed by Oil red staining and BIODIPY fluorescent staining as well as cholesterol-ester quantification by commercial kit. Cholesterol uptake and expression of scavenger receptors were detected by flow-cytometry. Cholesterol efflux capacity was measured by fluorescent plate-reader and ABC transporters were detected by Western Blots. Cytokines were detected by ELISA in supernatants and normalized by cellular lysates. Key findings: Our results showed that metformin decreased oxidized low-density lipoprotein (Ox-LDL)-induced cholesterol accumulation and foam cell formation by increasing cholesterol efflux to HDL, which was associated with an upregulation of ABC transporter ABCG-1. Moreover, metformin increased Ox-LDL-impaired IL-10 secretion, an important anti-foam cell cytokine in atherosclerosis. Significance: Our data highlighted the therapeutic potential of targeting macrophage cholesterol efflux with new or existing drugs for the possible reduction of foam cell formation in the prevention and treatment of diabetesaccelerated atherosclerosis.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81570775]; Natural Science Foundation of Zhejiang Province of ChinaNatural Science Foundation of Zhejiang Province [LY13H290007]; Wenzhou Public Welfare Science and Technology Project [Y20170167]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
出版地	OXFORD
ISSN	0024-3205
EISSN	1879-0631
卷号	216 页码:67-74
DOI	10.1016/j.lfs.2018.09.024
页数	8
WOS类目	Medicine, Research & Experimental ; Pharmacology & Pharmacy
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
WOS记录号	WOS:000453245300008
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
Pubmed记录号	30218721
Scopus记录号	2-s2.0-85056779264
通讯作者地址	[Gao, Qian]Medical School of Nanjing University,Nanjing,210093,China
scopus学科分类	Biochemistry, Genetics and Molecular Biology (all);Pharmacology, Toxicology and Pharmaceutics (all)
引用统计	被引频次：15[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/3856
专题	检验医学院（生命科学学院、生物学实验教学中心）_生物化学与分子生物学系基础医学院（机能实验教学中心）
通讯作者	Gao, Qian
作者单位	1.Medical School of Nanjing University,Nanjing,210093,China; 2.Department of Biochemistry,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou,325035,China
推荐引用方式 GB/T 7714	He, Xuan,Chen, Xiufang,Wang, Lei,et al. Metformin ameliorates Ox-LDL-induced foam cell formation in raw264.7 cells by promoting ABCG-1 mediated cholesterol efflux[J]. LIFE SCIENCES,2019,216:67-74.
APA	He, Xuan., Chen, Xiufang., Wang, Lei., Wang, Wenqing., Liang, Qiao., ... & Gao, Qian. (2019). Metformin ameliorates Ox-LDL-induced foam cell formation in raw264.7 cells by promoting ABCG-1 mediated cholesterol efflux. LIFE SCIENCES, 216, 67-74.
MLA	He, Xuan,et al."Metformin ameliorates Ox-LDL-induced foam cell formation in raw264.7 cells by promoting ABCG-1 mediated cholesterol efflux".LIFE SCIENCES 216(2019):67-74.