title: Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase.
abstract: OBJECTIVE
  A low level of high-density lipoprotein (HDL) in plasma has been recognized as an aspect of metabolic syndrome and as a crucial risk factor of cardiovascular events. However, the physiological regulation of plasma HDL levels has not been completely defined. Current studies aim to reveal the contribution of angiopoietin-like protein3 (angptl3), previously known as a plasma suppressor of lipoprotein lipase, to HDL metabolism.
  
  
  RESULTS
  Angptl3-deficient mice showed low plasma HDL cholesterol and HDL phospholipid (PL), and which were increased by ANGPTL3 supplementation via adenovirus. In vitro, ANGPTL3 inhibited the phospholipase activity of endothelial lipase (EL), which hydrolyzes HDL-PL and hence decreases plasma HDL levels, through a putative heparin-binding site in the N-terminal domain of ANGPTL3. Post-heparin plasma in Angptl3-knockout mice had higher phospholipase activity than did that in wild-type mice, suggesting that the activity of endogenous EL is elevated in Angptl3-deficient mice. Furthermore, we established an ELISA system for human ANGPTL3 and found that plasma ANGPTL3 levels significantly correlated with plasma HDL cholesterol and HDL-PL levels in human subjects.
  
  
  CONCLUSIONS
  Angptl3 acts as an inhibitor of EL and may be involved in the regulation of plasma HDL cholesterol and HDL-PL levels in humans and rodents.
authors.affiliation: Department of Medicine and Pathophysiology, Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Shimamura
authors.forename: Morihiro
authors.initials: M
authors.lastname: Matsuda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yasumo
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Okazaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Keita
authors.initials: K
authors.lastname: Kono
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shimizugawa
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ando
authors.forename: Ryuta
authors.initials: R
authors.lastname: Koishi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kohama
authors.forename: Naohiko
authors.initials: N
authors.lastname: Sakai
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kotani
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Komuro
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ishida
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Furukawa
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008049:Lipase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: C479896:ANGPTL3 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C404495:Angptl3 protein, mouse; D008076:Cholesterol, HDL; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; C410382:LIPG protein, human; D008049:Lipase; C498741:Lipg protein, mouse