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.