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

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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 languageEnglish
Pages (from-to)806-811
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume379
Issue number4
DOIs
Publication statusPublished - 20 Feb 2009
Externally publishedYes

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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