title: Endothelial lipase mediates HDL levels in normal and hyperlipidemic rabbits.
abstract: OBJECTIVE
  Existing evidence suggests that endothelial lipase (EL) plays an important role in high-densitylipoprotein (HDL) metabolism. Because rabbits are a useful animal model for the study of human lipid metabolism and atherosclerosis, we characterized rabbit EL (rEL) expression and investigated its relationship with plasma HDL levels in normal and hyperlipidemic rabbits.
  
  
  METHODS
  We cloned the rEL cDNA and analyzed the EL tissue expression using Northern blotting, real-time RT-PCR, Western blotting, and in situ hybridization. We evaluated the effects of rEL antisense on plasma HDL levels.
  
  
  RESULTS
  We found that rEL mRNA was highly expressed in cholesterol synthesis-related organs, including the liver, testis, and adrenal along with its expression in the lung, kidney, bone marrow, and small intestine. Interestingly, Watanabe heritable hyperlipidemic (WHHL) rabbits, a model of human familial hypercholesterolemia, had lower plasma levels of HDLs than normal rabbits. The plasma HDL levels in WHHL rabbits were inversely associated with high levels of plasma rEL proteins and hepatic expression of rEL mRNA. Injection of rEL-specific antisense oligonucleotides into rabbits resulted in the elevation of plasma large HDLs. Furthermore, we demonstrated that rEL mRNA was expressed by both endothelial cells and macrophages in the lesions of aortic atherosclerosis of WHHL rabbits.
  
  
  CONCLUSIONS
  rEL is expressed in multiple tissues and may have many physiological and pathophysiological functions, such as in the regulation of cholesterol metabolism and atherosclerosis. Our results suggest that EL is an important regulator of plasma HDL levels in rabbits.
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo-City, Japan.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.forename: Kae
authors.initials: K
authors.lastname: Nakamura
authors.forename: Tomonari
authors.initials: T
authors.lastname: Koike
authors.forename: Ahmed Bilal
authors.initials: AB
authors.lastname: Waqar
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Nishijima
authors.forename: Shuji
authors.initials: S
authors.lastname: Kitajima
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Qi
authors.forename: Jingwei
authors.initials: J
authors.lastname: Yu
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Graham
authors.forename: Rosanne M
authors.initials: RM
authors.lastname: Crooke
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishida
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Eva
authors.initials: E
authors.lastname: Hurt-Camejo
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D015153:Blotting, Western; D002871:Chromosome Banding; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000276:immunology; D017404:In Situ Hybridization, Fluorescence; D008049:Lipase / Q000037:antagonists & inhibitors / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000097:blood*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000493:pharmacokinetics; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D007074:Immunoglobulin G; D008075:Lipoproteins, HDL; D016376:Oligonucleotides, Antisense; D010446:Peptide Fragments; D012333:RNA, Messenger; D008049:Lipase