title: IRGM1 regulates oxidized LDL uptake by macrophage via actin-dependent receptor internalization during atherosclerosis.
abstract: Macrophage derived foam cells are actively involved in the initial phase of atherosclerosis. Uptake of modified lipoprotein such as oxidized LDL (oxLDL) is a critical step for foam cell formation. CD36 is the major receptor mediating oxLDL uptake by macrophage. However, the molecular mechanism underlying CD36 mediated oxLDL uptake remains unclear. Here we reported that IRGM1 (IRGM in human), a member of immunity-related small GTPase family, is essential for the actin-dependent CD36 mediated oxLDL uptake by macrophage. IRGM/IRGM1 was highly expressed by macrophage around the atherosclerotic plaque and was up-regulated by oxLDL both in vitro and in vivo. Moreover loss of IRGM/IRMG1 significantly decreased oxLDL uptake in both mouse and human. Furthermore, the IRGM1 knock-out mice displayed impaired CD36 internalization in macrophage, which was associated with the deficiency of F-actin polymerization. These results revealed a novel function of IRGM1 in regulating oxLDL uptake by macrophage during atherosclerosis.
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin 150081, China.
authors.forename: Fucan
authors.initials: F
authors.lastname: Xia
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.forename: Linlu
authors.initials: L
authors.lastname: Tian
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dong
authors.forename: Chunying
authors.initials: C
authors.lastname: Pei
authors.forename: Shuyu
authors.initials: S
authors.lastname: He
authors.forename: Pengyu
authors.initials: P
authors.lastname: Jiang
authors.forename: Hairong
authors.initials: H
authors.lastname: Cheng
authors.forename: Shaohong
authors.initials: S
authors.lastname: Fang
authors.forename: Hulun
authors.initials: H
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xu
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D004032:Diet / Q000009:adverse effects; D004705:Endocytosis / Q000502:physiology*; D005260:Female; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000199:Actins; D001057:Apolipoproteins E; D018955:CD36 Antigens; C096000:Ifi1 protein, mouse; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C099252:oxidized low density lipoprotein; D019204:GTP-Binding Proteins; C513539:IRGM protein, human