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

Biochem Biophys Res Commun. 2009 Feb 20;379(4):806-11. doi: 10.1016/j.bbrc.2008.12.018. Epub 2008 Dec 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-Like Protein 4
  • Angiopoietins / genetics*
  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Atherosclerosis / pathology
  • Cholesterol / blood
  • Foam Cells / immunology*
  • Lipid Metabolism / genetics*
  • Lipoproteins / blood
  • Macrophages, Peritoneal / immunology*
  • Mice
  • Mice, Knockout
  • Triglycerides / metabolism

Substances

  • Angiopoietin-Like Protein 4
  • Angiopoietins
  • Angptl4 protein, mouse
  • Apolipoproteins E
  • Lipoproteins
  • Triglycerides
  • Cholesterol