title: Macrophagic CD146 promotes foam cell formation and retention during atherosclerosis.
abstract: The persistence of cholesterol-engorged macrophages (foam cells) in the artery wall fuels the development of atherosclerosis. However, the mechanism that regulates the formation of macrophage foam cells and impedes their emigration out of inflamed plaques is still elusive. Here, we report that adhesion receptor CD146 controls the formation of macrophage foam cells and their retention within the plaque during atherosclerosis exacerbation. CD146 is expressed on the macrophages in human and mouse atheroma and can be upregulated by oxidized low-density lipoprotein (oxLDL). CD146 triggers macrophage activation by driving the internalization of scavenger receptor CD36 during lipid uptake. In response to oxLDL, macrophages show reduced migratory capacity toward chemokines CCL19 and CCL21; this capacity can be restored by blocking CD146. Genetic deletion of macrophagic CD146 or targeting of CD146 with an antibody result in much less complex plaques in high-fat diet-fed ApoE-/-mice by causing lipid-loaded macrophages to leave plaques. Collectively, our findings identify CD146 as a novel retention signal that traps macrophages within the artery wall, and a promising therapeutic target in atherosclerosis treatment.
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yongting
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Duan
authors.affiliation: Beijing Anzhen Hospital of the Capital University of Medical Sciences, Beijing 100029, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Beijing Anzhen Hospital of the Capital University of Medical Sciences, Beijing 100029, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Feng
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Dongling
authors.initials: D
authors.lastname: Yang
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiyun
authors.initials: X
authors.lastname: Yan
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D001854:Bone Marrow Cells / Q000473:pathology; D051929:CD146 Antigen / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism; D004705:Endocytosis; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology*; D017353:Gene Deletion; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008262:Macrophage Activation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000473:pathology; D011485:Protein Binding; D015854:Up-Regulation
chemical_list: D001057:Apolipoproteins E; D051929:CD146 Antigen; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein