PMID- 18258818
OWN - NLM
STAT- MEDLINE
DCOM- 20080317
LR  - 20080225
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 28
IP  - 3
DP  - 2008 Mar
TI  - In vivo arterial lipoprotein lipase expression augments inflammatory responses 
      and impairs vascular dilatation.
PG  - 455-62
LID - 10.1161/ATVBAHA.107.153239 [doi]
AB  - 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. METHODS AND 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.
FAU - Takahashi, Mayumi
AU  - Takahashi M
AD  - Department of Medicine, Columbia University College of Physicians & Surgeons, New 
      York, NY 10032, USA.
FAU - Hiyama, Yaeko
AU  - Hiyama Y
FAU - Yokoyama, Masayoshi
AU  - Yokoyama M
FAU - Yu, Shuiqing
AU  - Yu S
FAU - Hu, Yunying
AU  - Hu Y
FAU - Melford, Kristan
AU  - Melford K
FAU - Bensadoun, Andre
AU  - Bensadoun A
FAU - Goldberg, Ira J
AU  - Goldberg IJ
LA  - eng
GR  - HL45095/HL/NHLBI NIH HHS/United States
GR  - NHLBI 73029/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080207
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Lipoproteins, VLDL)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.1.1.34 (Lipoprotein Lipase)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Endothelial Cells/*physiology
MH  - Gene Expression
MH  - Genotype
MH  - Humans
MH  - Hypertriglyceridemia/complications/*enzymology/pathology
MH  - Immunohistochemistry
MH  - Lipoprotein Lipase/*biosynthesis/genetics
MH  - Lipoproteins, VLDL/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Random Allocation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
MH  - Triglycerides/metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Vasculitis/complications/*enzymology
MH  - Vasodilation/*physiology
EDAT- 2008/02/09 09:00
MHDA- 2008/03/18 09:00
CRDT- 2008/02/09 09:00
PHST- 2008/02/09 09:00 [pubmed]
PHST- 2008/03/18 09:00 [medline]
PHST- 2008/02/09 09:00 [entrez]
AID - ATVBAHA.107.153239 [pii]
AID - 10.1161/ATVBAHA.107.153239 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):455-62. doi: 
      10.1161/ATVBAHA.107.153239. Epub 2008 Feb 7.