Title | Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis |
Author | |
Corresponding Author | Chen,Y. Eugene; Guo,Yanhong |
Joint first author | Zhu,Wenzhen; Liang,Wenying |
Publication Years | 2022-09-01
|
DOI | |
Source Title | |
EISSN | 2073-4409
|
Volume | 11Issue:18 |
Abstract | Genetic variants in transmembrane 6 superfamily member 2 (TM6SF2), such as E167K, are associated with atherosclerotic cardiovascular disease (ASCVD). Chronic inflammation and lipid-laden macrophage foam cell formation are the central pathogeneses in the development of atherosclerosis. This study was undertaken to illustrate the biological function of TM6SF2 in macrophages and its role during atherosclerosis development. We generated myeloid cell-specific Tm6sf2 knockout mice on ApoE-deficient background (LysM Cre+/Tm6sf2/ApoE, TM6 mKO) with littermate LysM Cre−/Tm6sf2/ApoE (Control) mice as controls. Mice were fed a Western diet for 12 weeks to induce atherosclerosis. Myeloid Tm6sf2 deficiency inhibited atherosclerosis and decreased foam cells in the plaques without changing the plasma lipid profile. RNA sequencing of bone marrow-derived macrophages (BMDMs) from TM6 mKO mice demonstrated the downregulation of genes associated with inflammation, cholesterol uptake, and endoplasmic reticulum (ER) stress. TM6SF2 was upregulated by oxidized low-density lipoprotein (oxLDL) in macrophages. Silencing TM6SF2 in THP-1-derived macrophages and Tm6sf2 deficiency in BMDMs reduced inflammatory responses and ER stress and attenuated cholesterol uptake and foam cell formation, while the overexpression of TM6SF2 showed opposite effects. In conclusion, myeloid TM6SF2 deficiency inhibits atherosclerosis development and is a potential therapeutic target for the treatment of atherogenesis. |
Keywords | |
URL | [Source Record] |
Indexed By | |
Language | English
|
SUSTech Authorship | Non-SUSTech
|
Funding Project | Center for Information Technology[HL134569]
; Center for Scientific Review[HL134569]
; National Institutes of Health[HL134569]
; Office of Extramural Research, National Institutes of Health[HL134569]
; Office of Research Infrastructure Programs, National Institutes of Health[HL134569]
; Center for Information Technology[HL137214]
; Center for Scientific Review[HL137214]
; National Institutes of Health[HL137214]
; Office of Extramural Research, National Institutes of Health[HL137214]
; Office of Research Infrastructure Programs, National Institutes of Health[HL137214]
; Center for Information Technology[HL138139]
; Center for Scientific Review[HL138139]
; National Institutes of Health[HL138139]
; Office of Extramural Research, National Institutes of Health[HL138139]
; Office of Research Infrastructure Programs, National Institutes of Health[HL138139]
; Center for Information Technology[HL151524]
; Center for Scientific Review[HL151524]
; National Institutes of Health[HL151524]
; Office of Extramural Research, National Institutes of Health[HL151524]
; Office of Research Infrastructure Programs, National Institutes of Health[HL151524]
; Center for Information Technology[HL159871]
; Center for Scientific Review[HL159871]
; National Institutes of Health[HL159871]
; Office of Extramural Research, National Institutes of Health[HL159871]
; Office of Research Infrastructure Programs, National Institutes of Health[HL159871]
|
WOS Research Area | Cell Biology
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WOS Subject | Cell Biology
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WOS Accession No | WOS:000858198600001
|
Publisher | |
Scopus EID | 2-s2.0-85138652424
|
Data Source | Scopus
|
Citation statistics |
Cited Times [WOS]:0
|
Document Type | Journal Article |
Identifier | http://kc.sustech.edu.cn/handle/2SGJ60CL/402714 |
Department | Department of Pharmacology |
Affiliation | 1.Department of Internal Medicine, Frankel Cardiovascular Center,University of Michigan,Ann Arbor,48109,United States 2.Department of Pharmacology, Southern University of Science and Technology,Shenzhen,518055,China |
Recommended Citation GB/T 7714 |
Zhu,Wenzhen,Liang,Wenying,Lu,Haocheng,et al. Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis[J]. Cells,2022,11(18).
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APA |
Zhu,Wenzhen.,Liang,Wenying.,Lu,Haocheng.,Chang,Lin.,Zhang,Jifeng.,...&Guo,Yanhong.(2022).Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis.Cells,11(18).
|
MLA |
Zhu,Wenzhen,et al."Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis".Cells 11.18(2022).
|
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