Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis

被引：75

作者：

Adachi, Hironori ^{[2
]}

Fujiwara, Yukio ^{[3
]}

Kondo, Tatsuya ^{[2
]}

Nishikawa, Takeshi ^{[2
]}

Ogawa, Rei ^{[4
]}

Matsumura, Takeshi ^{[2
]}

Ishii, Norio ^{[2
]}

Nagai, Ryoji ^{[5
]}

Miyata, Keishi ^{[1
]}

Tabata, Mitsuhisa ^{[1
]}

Motoshima, Hiroyuki ^{[2
]}

Furukawa, Noboru ^{[2
]}

Tsuruzoe, Kaku ^{[2
]}

Kawashima, Junji ^{[2
]}

Takeya, Motohiro ^{[3
]}

Yamashita, Shizuya ^{[6
]}

Koh, Gou Young ^{[7
]}

Nagy, Andras ^{[8
]}

Suda, Toshio ^{[9
]}

Oike, Yuichi ^{[1
]}

Araki, Eiichi ^{[2
]}

机构：

[1] Kumamoto Univ, Dept Mol Genet, Fac Med & Pharmaceut Sci, Kumamoto 8608556, Japan

[2] Kumamoto Univ, Dept Metab Med, Fac Med & Pharmaceut Sci, Kumamoto 8608556, Japan

[3] Kumamoto Univ, Dept Cell Pathol, Fac Med & Pharmaceut Sci, Kumamoto 8608556, Japan

[4] Prefectural Univ Kumamoto, Dept Environm & Symbiot Sci, Kumamoto 8628502, Japan

[5] Kumamoto Univ, Dept Med Biochem, Fac Med & Pharmaceut Sci, Kumamoto 8608556, Japan

[6] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Suita, Osaka 5650871, Japan

[7] Korea Adv Inst Sci & Technol, Biomed Ctr, Dept Biol Sci, Taejon 305701, South Korea

[8] Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada

[9] Keio Univ, Sch Med, Dept Cell Differentiat, Sakaguchi Lab, Tokyo 1608582, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 379卷 / 04期

基金：

日本学术振兴会;

关键词：

Angptl; 4; Knockout mice; Apolipoprotein E; Atherosclerosis; Lipid metabolism; Lipoprotein lipase; Postprandial hypertriglyceridemia; Macrophage; Foam cells; Foam cell formation; Oxidized low-density lipoprotein; LOW-DENSITY-LIPOPROTEIN; ANGIOPOIETIN-LIKE PROTEIN-4; KNOCKOUT MICE; LIPASE; CHOLESTEROL; OVEREXPRESSION; RECEPTOR; RABBITS; PLASMA; HDL;

D O I：

10.1016/j.bbrc.2008.12.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：806 / 811

页数：6

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