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

Hironori Adachi; Yukio Fujiwara; Tatsuya Kondo; Takeshi Nishikawa; Rei Ogawa; Takeshi Matsumura; Norio Ishii; Ryoji Nagai; Keishi Miyata; Mitsuhisa Tabata; Hiroyuki Motoshima; Noboru Furukawa; Kaku Tsuruzoe; Junji Kawashima; Motohiro Takeya; Shizuya Yamashita; Gou Young Koh; Andras Nagy; Toshio Suda; Yuichi Oike; Eiichi Araki

doi:10.1016/j.bbrc.2008.12.018

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

Hironori Adachi, Yukio Fujiwara, Tatsuya Kondo, Takeshi Nishikawa, Rei Ogawa, Takeshi Matsumura, Norio Ishii, Ryoji Nagai, Keishi Miyata, Mitsuhisa Tabata, Hiroyuki Motoshima, Noboru Furukawa, Kaku Tsuruzoe, Junji Kawashima, Motohiro Takeya, Shizuya Yamashita, Gou Young Koh, Andras Nagy, Toshio Suda, Yuichi OikeEiichi Araki

Research output: Contribution to journal › Article › Research › peer-review

66 Citations (Scopus)

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.

Original language	English
Pages (from-to)	806-811
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	379
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.12.018
Publication status	Published - 20 Feb 2009
Externally published	Yes

Keywords

Angptl 4
Apolipoprotein E
Atherosclerosis
Foam cell formation
Foam cells
Knockout mice
Lipid metabolism
Lipoprotein lipase
Macrophage
Oxidized low-density lipoprotein
Postprandial hypertriglyceridemia

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Adachi, H., Fujiwara, Y., Kondo, T., Nishikawa, T., Ogawa, R., Matsumura, T., Ishii, N., Nagai, R., Miyata, K., Tabata, M., Motoshima, H., Furukawa, N., Tsuruzoe, K., Kawashima, J., Takeya, M., Yamashita, S., Koh, G. Y., Nagy, A., Suda, T., ... Araki, E. (2009). Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis. Biochemical and Biophysical Research Communications, 379(4), 806-811. https://doi.org/10.1016/j.bbrc.2008.12.018

@article{8c04de4f37ab411381eaedf661b59416,

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.",

keywords = "Angptl 4, Apolipoprotein E, Atherosclerosis, Foam cell formation, Foam cells, Knockout mice, Lipid metabolism, Lipoprotein lipase, Macrophage, Oxidized low-density lipoprotein, Postprandial hypertriglyceridemia",

author = "Hironori Adachi and Yukio Fujiwara and Tatsuya Kondo and Takeshi Nishikawa and Rei Ogawa and Takeshi Matsumura and Norio Ishii and Ryoji Nagai and Keishi Miyata and Mitsuhisa Tabata and Hiroyuki Motoshima and Noboru Furukawa and Kaku Tsuruzoe and Junji Kawashima and Motohiro Takeya and Shizuya Yamashita and Koh, {Gou Young} and Andras Nagy and Toshio Suda and Yuichi Oike and Eiichi Araki",

year = "2009",

month = feb,

day = "20",

doi = "10.1016/j.bbrc.2008.12.018",

language = "English",

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Adachi, H, Fujiwara, Y, Kondo, T, Nishikawa, T, Ogawa, R, Matsumura, T, Ishii, N, Nagai, R, Miyata, K, Tabata, M, Motoshima, H, Furukawa, N, Tsuruzoe, K, Kawashima, J, Takeya, M, Yamashita, S, Koh, GY, Nagy, A, Suda, T, Oike, Y & Araki, E 2009, 'Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis', Biochemical and Biophysical Research Communications, vol. 379, no. 4, pp. 806-811. https://doi.org/10.1016/j.bbrc.2008.12.018

TY - JOUR

T1 - Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis

AU - Adachi, Hironori

AU - Fujiwara, Yukio

AU - Kondo, Tatsuya

AU - Nishikawa, Takeshi

AU - Ogawa, Rei

AU - Matsumura, Takeshi

AU - Ishii, Norio

AU - Nagai, Ryoji

AU - Miyata, Keishi

AU - Tabata, Mitsuhisa

AU - Motoshima, Hiroyuki

AU - Furukawa, Noboru

AU - Tsuruzoe, Kaku

AU - Kawashima, Junji

AU - Takeya, Motohiro

AU - Yamashita, Shizuya

AU - Koh, Gou Young

AU - Nagy, Andras

AU - Suda, Toshio

AU - Oike, Yuichi

AU - Araki, Eiichi

PY - 2009/2/20

Y1 - 2009/2/20

N2 - 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.

AB - 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.

KW - Angptl 4

KW - Apolipoprotein E

KW - Atherosclerosis

KW - Foam cell formation

KW - Foam cells

KW - Knockout mice

KW - Lipid metabolism

KW - Lipoprotein lipase

KW - Macrophage

KW - Oxidized low-density lipoprotein

KW - Postprandial hypertriglyceridemia

UR - http://www.scopus.com/inward/record.url?scp=58949083661&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2008.12.018

DO - 10.1016/j.bbrc.2008.12.018

M3 - Article

C2 - 19094966

AN - SCOPUS:58949083661

VL - 379

SP - 806

EP - 811

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -

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

Abstract

Keywords

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