Abstract
Objective:
Vascular endothelial growth factor (VEGF) is upregulated after arterial injury. Its role in the pathogenesis of neointimal formation after periadventitial injury, however, has not been addressed.
Methods and results:
Expression of VEGF and its receptors but not that of placental growth factor markedly increased with the development of neointimal formation in hypercholesterolemic mice after cuff-induced periarterial injury. Transfection with the murine soluble Flt-1 (sFlt-1) gene to block VEGF in vivo in mice inhibited early inflammation and later neointimal formation. The sFlt-1 gene transfer did not affect plasma lipid levels but attenuated increased expression of VEGF, Flt-1, Flk-1, monocyte chemoattractant protein-1, and other inflammation-promoting factors. Mice with Flt-1 kinase deficiency also displayed reduced neointimal formation.
Conclusions:
Inflammatory changes mediated by VEGF and Flt-1 signals play an important role in the pathogenesis of neointimal formation after cuff-induced periadventitial injury. VEGF might promote neointimal formation by acting as a proinflammatory cytokine.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apolipoproteins E / deficiency
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Apolipoproteins E / physiology
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Femoral Artery / chemistry
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Femoral Artery / injuries
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Femoral Artery / metabolism
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Gene Expression Regulation / genetics
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Gene Transfer Techniques
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Hyperplasia / blood
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Hyperplasia / enzymology
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Immunohistochemistry / methods
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Lipids / blood
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neovascularization, Physiologic / physiology*
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Protein Isoforms / genetics
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Signal Transduction / physiology*
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Solubility
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Time Factors
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Tunica Intima / pathology
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Tunica Intima / physiology*
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Vascular Endothelial Growth Factor Receptor-1 / deficiency
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Vascular Endothelial Growth Factor Receptor-1 / genetics
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Vascular Endothelial Growth Factor Receptor-1 / immunology
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Vascular Endothelial Growth Factor Receptor-1 / metabolism*
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Vascular Endothelial Growth Factor Receptor-2 / biosynthesis
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Vascular Endothelial Growth Factor Receptor-2 / immunology
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Vascular Endothelial Growth Factors / genetics
Substances
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Apolipoproteins E
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Lipids
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Protein Isoforms
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Vascular Endothelial Growth Factors
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2