PMID- 20947823
OWN - NLM
STAT- MEDLINE
DCOM- 20110120
LR  - 20211020
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 31
IP  - 1
DP  - 2011 Jan
TI  - Increase in GLUT1 in smooth muscle alters vascular contractility and increases 
      inflammation in response to vascular injury.
PG  - 86-94
LID - 10.1161/ATVBAHA.110.215004 [doi]
AB  - OBJECTIVE: The goal of this study was to test the contributing role of increasing 
      glucose uptake in vascular smooth muscle cells (VSMCs) in vascular complications 
      and disease. METHODS AND RESULTS: A murine genetic model was established in which 
      glucose trasporter 1 (GLUT1), the non-insulin-dependent glucose transporter 
      protein, was overexpressed in smooth muscle using the sm22alpha promoter. 
      Overexpression of GLUT1 in smooth muscle led to significant increases in glucose 
      uptake (n=3, P<0.0001) as measured using radiolabeled 2-deoxyglucose. Fasting 
      blood glucose, insulin, and nonesterified fatty acids were unchanged. 
      Contractility in aortic ring segments was decreased in sm22alpha-GLUT1 mice (n=10, 
      P<0.04). In response to vascular injury, sm22alpha-GLUT1 mice exhibited a 
      proinflammatory phenotype, including a significant increase in the percentage of 
      neutrophils in the lesion (n=4, P<0.04) and an increase in monocyte 
      chemoattractant protein-1 (MCP-1) immunofluorescence. Circulating haptoglobin and 
      glutathione/total glutathione were significantly higher in the sm22alpha-GLUT1 mice 
      postinjury compared with controls (n=4, P<0.05), suggesting increased flux 
      through the pentose phosphate pathway. sm22alpha-GLUT1 mice exhibited significant 
      medial hypertrophy following injury that was associated with a significant 
      increase in the percentage of VSMCs in the media staining positive for nuclear 
      phosphoSMAD2/3 (n=4, P<0.003). CONCLUSIONS: In summary, these findings suggest 
      that increased glucose uptake in VSMCs impairs vascular contractility and 
      accelerates a proinflammatory, neutrophil-rich lesion in response to injury, as 
      well as medial hypertrophy, which is associated with enhanced transforming growth 
      factor-beta activity.
FAU - Adhikari, Neeta
AU  - Adhikari N
AD  - University of Minnesota, Minneapolis, MN 55455, USA.
FAU - Basi, David L
AU  - Basi DL
FAU - Carlson, Marjorie
AU  - Carlson M
FAU - Mariash, Ami
AU  - Mariash A
FAU - Hong, Zhigang
AU  - Hong Z
FAU - Lehman, Ute
AU  - Lehman U
FAU - Mullegama, Sureni
AU  - Mullegama S
FAU - Weir, Edward K
AU  - Weir EK
FAU - Hall, Jennifer L
AU  - Hall JL
LA  - eng
GR  - R01 HL065322/HL/NHLBI NIH HHS/United States
GR  - R21 DK078029/DK/NIDDK NIH HHS/United States
GR  - R21 DK078029-02/DK/NIDDK NIH HHS/United States
GR  - R01 HL-65322/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101014
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Blood Glucose)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Haptoglobins)
RN  - 0 (Insulin)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (SLC2A1 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, mouse)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, mouse)
RN  - 0 (transgelin)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Aorta/metabolism/physiopathology
MH  - Blood Glucose/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Deoxyglucose/metabolism
MH  - Disease Models, Animal
MH  - Fatty Acids, Nonesterified/blood
MH  - Femoral Artery/injuries/metabolism
MH  - Glucose Transporter Type 1/genetics/*metabolism
MH  - Glutathione/blood
MH  - Haptoglobins/metabolism
MH  - Humans
MH  - Hypertrophy
MH  - Inflammation/*etiology/metabolism/pathology
MH  - Insulin/blood
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microfilament Proteins/genetics
MH  - Muscle Proteins/genetics
MH  - Muscle, Smooth, Vascular/injuries/*metabolism/pathology/physiopathology
MH  - Myocytes, Smooth Muscle/*metabolism/pathology
MH  - Neutrophil Infiltration
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - Smad2 Protein/metabolism
MH  - Smad3 Protein/metabolism
MH  - Up-Regulation
MH  - *Vasoconstriction
PMC - PMC3014530
MID - NIHMS252810
EDAT- 2010/10/16 06:00
MHDA- 2011/01/21 06:00
PMCR- 2012/01/01
CRDT- 2010/10/16 06:00
PHST- 2010/10/16 06:00 [entrez]
PHST- 2010/10/16 06:00 [pubmed]
PHST- 2011/01/21 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - ATVBAHA.110.215004 [pii]
AID - 10.1161/ATVBAHA.110.215004 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):86-94. doi: 
      10.1161/ATVBAHA.110.215004. Epub 2010 Oct 14.