Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis.
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.
Adachi
Hironori
H
Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Fujiwara
Yukio
Y
Kondo
Tatsuya
T
Nishikawa
Takeshi
T
Ogawa
Rei
R
Matsumura
Takeshi
T
Ishii
Norio
N
Nagai
Ryoji
R
Miyata
Keishi
K
Tabata
Mitsuhisa
M
Motoshima
Hiroyuki
H
Furukawa
Noboru
N
Tsuruzoe
Kaku
K
Kawashima
Junji
J
Takeya
Motohiro
M
Yamashita
Shizuya
S
Koh
Gou Young
GY
Nagy
Andras
A
Suda
Toshio
T
Oike
Yuichi
Y
Araki
Eiichi
E
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
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D001057:Apolipoproteins E; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol