title: Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis.
abstract: Angiopoietin-like protein family 4 (Angptl 4) has been shown to regulate lipoprotein metabolism through the inhibition of lipoprotein lipase (LPL). We generated ApoE(-/-)Angptl 4(-/-) mice to study the effect of Angptl 4 deficiency on lipid metabolism and atherosclerosis. Fasting and postolive oil-loaded triglyceride (TG) levels were largely decreased in ApoE(-/-)Angptl 4(-/-) mice compared with and ApoE(-/-)Angptl 4(+/+) mice. There was a significant (75+/-12%) reduction in atherosclerotic lesion size in ApoE(-/-)Angptl 4(-/-) mice compared with ApoE(-/-) Angptl 4(+/+) mice. Peritoneal macrophages, isolated from Angptl 4(-/-) mice to investigate the foam cell formation, showed a significant decrease in newly synthesized cholesteryl ester (CE) accumulation induced by acetyl low-density lipoprotein (acLDL) compared with those from Angptl 4(+/+) mice. Thus, genetic knockout of Angptl 4 protects ApoE(-/-) mice against development and progression of atherosclerosis and strongly suppresses the ability of the macrophages to become foam cells in vitro.
authors.affiliation: Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Adachi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kondo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Rei
authors.initials: R
authors.lastname: Ogawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumura
authors.forename: Norio
authors.initials: N
authors.lastname: Ishii
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nagai
authors.forename: Keishi
authors.initials: K
authors.lastname: Miyata
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Tabata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Motoshima
authors.forename: Noboru
authors.initials: N
authors.lastname: Furukawa
authors.forename: Kaku
authors.initials: K
authors.lastname: Tsuruzoe
authors.forename: Junji
authors.initials: J
authors.lastname: Kawashima
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D005487:Foam Cells / Q000276:immunology*; D050356:Lipid Metabolism / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D001057:Apolipoproteins E; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol