中文版 | English
Title

Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis

Author
Corresponding AuthorChen,Y. Eugene; Guo,Yanhong
Joint first authorZhu,Wenzhen; Liang,Wenying
Publication Years
2022-09-01
DOI
Source Title
EISSN
2073-4409
Volume11Issue: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
WOS Subject
Cell Biology
WOS Accession No
WOS:000858198600001
Publisher
Scopus EID
2-s2.0-85138652424
Data Source
Scopus
Citation statistics
Cited Times [WOS]:0
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/402714
DepartmentDepartment 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).
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).
Files in This Item:
File Name/Size DocType Version Access License
Myeloid TM6SF2 Defic(1775KB) Open Access--View
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Export to Excel
Export to Csv
Altmetrics Score
Google Scholar
Similar articles in Google Scholar
[Zhu,Wenzhen]'s Articles
[Liang,Wenying]'s Articles
[Lu,Haocheng]'s Articles
Baidu Scholar
Similar articles in Baidu Scholar
[Zhu,Wenzhen]'s Articles
[Liang,Wenying]'s Articles
[Lu,Haocheng]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Zhu,Wenzhen]'s Articles
[Liang,Wenying]'s Articles
[Lu,Haocheng]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis.pdf
Format: Adobe PDF
File name: Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis.pdf
Format: Adobe PDF
No comment.

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.