title: In vivo arterial lipoprotein lipase expression augments inflammatory responses and impairs vascular dilatation.
abstract: OBJECTIVE
  Although epidemiologic data suggest that hypertriglyceridemia and elevated plasma levels of fatty acids are toxic to arteries, in vitro correlates have been inconsistent. To investigate whether increased endothelial cell expression of lipoprotein lipase (LpL), the primary enzyme creating free fatty acids from circulating triglycerides (TG), affects vascular function, we created transgenic mice that express human LpL (hLpL) driven by the promoter and enhancer of the Tie2 receptor.
  
  
  RESULTS
  Mice expressing this transgene, denoted EC-hLpL and L for low and H for high expression, had decreased plasma TG levels compared with wild-type mice (WT): 106+/-31 in WT, 37+/-17 (line H), and 63+/-31 mg/dL (line L) because of a reduction in VLDL TG; plasma cholesterol and HDL levels were unaltered. Crossing a high expressing EC-hLpL transgene onto the LpL knockout background allowed for survival of the pups; TG in these mice was approximately equal to that of heterozygous LpL knockout mice. Surprisingly, under control conditions the EC-hLpL transgene did not alter arterial function or endothelial cell gene expression; however, after tumor necrosis factor (TNF)-alpha treatment, arterial vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and endogenous TNF-alpha mRNA levels were increased and arteries had impaired endothelium-dependent vasodilatation. This was associated with reduced eNOS dimers.
  
  
  CONCLUSIONS
  Therefore, we hypothesize that excess vascular wall LpL augments vascular dysfunction in the setting of inflammation.
authors.affiliation: Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yaeko
authors.initials: Y
authors.lastname: Hiyama
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Yu
authors.forename: Yunying
authors.initials: Y
authors.lastname: Hu
authors.forename: Kristan
authors.initials: K
authors.lastname: Melford
authors.forename: André
authors.initials: A
authors.lastname: Bensadoun
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D008071:Lipoprotein Lipase / Q000096:biosynthesis* / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014657:Vasculitis / Q000150:complications / Q000201:enzymology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D008079:Lipoproteins, VLDL; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase