Methyl tertiary-butyl ether inhibits THP-1 macrophage cholesterol efflux in vitro and accelerates atherosclerosis in ApoE-deficient mice in vivo

Ren，Qidong1,2; Xie，Xinni1; Tang，Yue1,2; Hu，Qing3; Du，Yuguo1,2

2021-03-01

10.1016/j.jes.2020.08.011

Journal of Environmental Sciences   影响因子和分区

1001-0742

1878-7320

The biosafety of methyl tertiary-butyl ether (MTBE), mainly used as a gasoline additive, has long been a contentious topic. In addition to its routine toxicities, MTBE has been demonstrated to disrupt glucose and lipid metabolism and contribute to the development of type 2 diabetes as well as obesity. As one of the morbidities related to dyslipidemia, atherosclerosis is worthy of being investigated under MTBE exposure. Since foam cells derived from macrophages play pivotal roles during atherosclerosis development, we studied the effects of MTBE on macrophages in vitro and assessed the effect of MTBE on atherosclerosis plaque formation with the ApoE mouse model in vivo for the first time. Our results demonstrated that exposure to MTBE at environmentally relevant concentrations decreased the expression of ABCA1 and ABCG1, which are responsible for macrophage cholesterol efflux, at both mRNA and protein levels in THP-1 macrophages. Consequently, treatment with MTBE inhibited the transport of cholesterol from macrophages to High-density lipoprotein. ApoE mice exposed to MTBE at environmentally relevant concentrations (100, 1000 μg/kg) displayed significant increases in lesion area in the aorta and aortic root compared to vehicle-treated ones. Further analysis indicated that MTBE exposure enhanced the macrophage-specific marker Mac-2 contents within plaques in the aortic root, implying that MTBE could promote macrophage-derived foam cell formation and thus accelerate atherosclerosis plaque formation. We for the first time demonstrated the pro-atherogenic effect of MTBE via eliciting disruption of macrophage cholesterol efflux and accelerating foam cell formation and atherosclerosis plaque development.

ApoE−/− mouse Atherosclerosis cholesterol efflux macrophage Methyl tertiary‑butyl ether (MTBE)

SCI ; EI

英语

其他

National Key R&D Program of China["2019YFC1605800","2018YFC0406302"] ; National Natural Science Foundation of China[21806179,21672255] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB14040201]

Environmental Sciences & Ecology

Environmental Sciences

WOS:000598914600020

SCIENCE PRESS

20203609130663

Diseases ; Ethers ; Cholesterol ; Mammals ; Blood vessels

Biological Materials and Tissue Engineering:461.2 ; Immunology:461.9.1 ; Organic Compounds:804.1

2-s2.0-85090036470

Scopus

1.State Key Laboratory of Environmental Chemistry and Eco-Toxicology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing,100085,China
2.College of Resources and Environment,University of Chinese Academy of Sciences,Beijing,100049,China
3.School of Environmental Science and Engineering,Southern University of Science and Technology,Shenzhen,518055,China

Ren，Qidong,Xie，Xinni,Tang，Yue,et al. Methyl tertiary-butyl ether inhibits THP-1 macrophage cholesterol efflux in vitro and accelerates atherosclerosis in ApoE-deficient mice in vivo[J]. Journal of Environmental Sciences,2021,101:236-247.

Ren，Qidong,Xie，Xinni,Tang，Yue,Hu，Qing,&Du，Yuguo.(2021).Methyl tertiary-butyl ether inhibits THP-1 macrophage cholesterol efflux in vitro and accelerates atherosclerosis in ApoE-deficient mice in vivo.Journal of Environmental Sciences,101,236-247.

Ren，Qidong,et al."Methyl tertiary-butyl ether inhibits THP-1 macrophage cholesterol efflux in vitro and accelerates atherosclerosis in ApoE-deficient mice in vivo".Journal of Environmental Sciences 101(2021):236-247.