Vascular endothelial growth factor is necessary in the development of arteriosclerosis by recruiting/activating monocytes in a rat model of long-term inhibition of nitric oxide synthesis

Qingwei Zhao

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129 Citations (Scopus)

Abstract

BACKGROUND: It remains unclear whether vascular endothelial growth factor (VEGF) is a proarteriosclerotic or an antiarteriosclerotic factor. We recently reported that long-term inhibition of nitric oxide by administering Nomega-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular inflammation and arteriosclerosis. METHODS AND RESULTS: We used this animal model to investigate the role of VEGF in arteriosclerosis. We blocked VEGF activity in vivo by transfecting with plasmid DNA encoding the murine soluble FLT-1 (sFLT-1) gene into thigh muscle. Soluble FLT-1 can suppress VEGF activity both by sequestering VEGF and by functioning as a dominant-negative inhibitor of VEGF receptors. We observed vascular inflammation associated with increased VEGF expression within 3 days of L-NAME administration, which was prevented by pretreatment with ACE inhibitor, angiotensin II receptor antagonist, or neutralizing monocyte chemoattractant protein-1 antibody. The sFLT-1 gene transfer attenuated the early vascular inflammation and prevented late arteriosclerosis. The sFLT-1 gene transfer also inhibited increased expression of monocyte chemoattractant protein-1 and transforming growth factor-beta, indicating creation of a positive feedback loop to cause arteriosclerosis. CONCLUSIONS: VEGF is necessary in the development of arteriosclerosis by mediating monocyte recruitment and activation in this model.
Original languageEnglish
Pages (from-to)1110-1115
JournalCirculation
Volume105
StatePublished - Mar 5 2002

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Arteriosclerosis
Vascular Endothelial Growth Factor A
Monocytes
Nitric Oxide
Blood Vessels
Chemokine CCL2
NG-Nitroarginine Methyl Ester
Inflammation
Genes
Vascular Endothelial Growth Factor Receptor
Angiotensin Receptor Antagonists
Thigh
Angiotensin-Converting Enzyme Inhibitors
Transforming Growth Factor beta
Coronary Artery Disease
Plasmids
Animal Models
Muscles
Antibodies
DNA

Cite this

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title = "Vascular endothelial growth factor is necessary in the development of arteriosclerosis by recruiting/activating monocytes in a rat model of long-term inhibition of nitric oxide synthesis",
abstract = "BACKGROUND: It remains unclear whether vascular endothelial growth factor (VEGF) is a proarteriosclerotic or an antiarteriosclerotic factor. We recently reported that long-term inhibition of nitric oxide by administering Nomega-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular inflammation and arteriosclerosis. METHODS AND RESULTS: We used this animal model to investigate the role of VEGF in arteriosclerosis. We blocked VEGF activity in vivo by transfecting with plasmid DNA encoding the murine soluble FLT-1 (sFLT-1) gene into thigh muscle. Soluble FLT-1 can suppress VEGF activity both by sequestering VEGF and by functioning as a dominant-negative inhibitor of VEGF receptors. We observed vascular inflammation associated with increased VEGF expression within 3 days of L-NAME administration, which was prevented by pretreatment with ACE inhibitor, angiotensin II receptor antagonist, or neutralizing monocyte chemoattractant protein-1 antibody. The sFLT-1 gene transfer attenuated the early vascular inflammation and prevented late arteriosclerosis. The sFLT-1 gene transfer also inhibited increased expression of monocyte chemoattractant protein-1 and transforming growth factor-beta, indicating creation of a positive feedback loop to cause arteriosclerosis. CONCLUSIONS: VEGF is necessary in the development of arteriosclerosis by mediating monocyte recruitment and activation in this model.",
author = "Qingwei Zhao",
year = "2002",
month = "3",
day = "5",
language = "English",
volume = "105",
pages = "1110--1115",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",

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TY - JOUR

T1 - Vascular endothelial growth factor is necessary in the development of arteriosclerosis by recruiting/activating monocytes in a rat model of long-term inhibition of nitric oxide synthesis

AU - Zhao, Qingwei

PY - 2002/3/5

Y1 - 2002/3/5

N2 - BACKGROUND: It remains unclear whether vascular endothelial growth factor (VEGF) is a proarteriosclerotic or an antiarteriosclerotic factor. We recently reported that long-term inhibition of nitric oxide by administering Nomega-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular inflammation and arteriosclerosis. METHODS AND RESULTS: We used this animal model to investigate the role of VEGF in arteriosclerosis. We blocked VEGF activity in vivo by transfecting with plasmid DNA encoding the murine soluble FLT-1 (sFLT-1) gene into thigh muscle. Soluble FLT-1 can suppress VEGF activity both by sequestering VEGF and by functioning as a dominant-negative inhibitor of VEGF receptors. We observed vascular inflammation associated with increased VEGF expression within 3 days of L-NAME administration, which was prevented by pretreatment with ACE inhibitor, angiotensin II receptor antagonist, or neutralizing monocyte chemoattractant protein-1 antibody. The sFLT-1 gene transfer attenuated the early vascular inflammation and prevented late arteriosclerosis. The sFLT-1 gene transfer also inhibited increased expression of monocyte chemoattractant protein-1 and transforming growth factor-beta, indicating creation of a positive feedback loop to cause arteriosclerosis. CONCLUSIONS: VEGF is necessary in the development of arteriosclerosis by mediating monocyte recruitment and activation in this model.

AB - BACKGROUND: It remains unclear whether vascular endothelial growth factor (VEGF) is a proarteriosclerotic or an antiarteriosclerotic factor. We recently reported that long-term inhibition of nitric oxide by administering Nomega-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular inflammation and arteriosclerosis. METHODS AND RESULTS: We used this animal model to investigate the role of VEGF in arteriosclerosis. We blocked VEGF activity in vivo by transfecting with plasmid DNA encoding the murine soluble FLT-1 (sFLT-1) gene into thigh muscle. Soluble FLT-1 can suppress VEGF activity both by sequestering VEGF and by functioning as a dominant-negative inhibitor of VEGF receptors. We observed vascular inflammation associated with increased VEGF expression within 3 days of L-NAME administration, which was prevented by pretreatment with ACE inhibitor, angiotensin II receptor antagonist, or neutralizing monocyte chemoattractant protein-1 antibody. The sFLT-1 gene transfer attenuated the early vascular inflammation and prevented late arteriosclerosis. The sFLT-1 gene transfer also inhibited increased expression of monocyte chemoattractant protein-1 and transforming growth factor-beta, indicating creation of a positive feedback loop to cause arteriosclerosis. CONCLUSIONS: VEGF is necessary in the development of arteriosclerosis by mediating monocyte recruitment and activation in this model.

M3 - Article

VL - 105

SP - 1110

EP - 1115

JO - Circulation

JF - Circulation

SN - 0009-7322

ER -