Soluble Flt-1 Gene Transfer Ameliorates Neointima Formation After Wire Injury in flt-1 Tyrosine Kinase-Deficient Mice

We have demonstrated that vascular endothelial growth factor (VEGF) expression is upregulated in injured vascular wall, and blockade of VEGF inhibited monocyte infiltration and neointima formation in several animal models. In the present study, we aimed to clarify relative role of two VEGF receptors...

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Veröffentlicht in:	Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2009-04, Vol.29 (4), p.458-464
Hauptverfasser:	KOGA, Jun-Ichiro, MATOBA, Tetsuya, EGASHIRA, Kensuke, KUBO, Mitsuki, MIYAGAWA, Miho, IWATA, Eiko, SUEISHI, Katsuo, SHIBUYA, Masabumi, SUNAGAWA, Kenji
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Associated diseases and complications Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cell Proliferation Cells, Cultured Chemokine CCL2 - metabolism Chemotaxis, Leukocyte Constriction, Pathologic Diabetes. Impaired glucose tolerance Disease Models, Animal Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Electroporation Endocrine pancreas. Apud cells (diseases) Endocrinopathies Femoral Artery - enzymology Femoral Artery - injuries Femoral Artery - pathology Gene Transfer Techniques Hyperplasia Macrophages, Peritoneal - enzymology Male Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Muscle, Smooth, Vascular - enzymology Muscle, Smooth, Vascular - injuries Muscle, Smooth, Vascular - pathology Myocytes, Smooth Muscle - enzymology Neovascularization, Physiologic Tissue Culture Techniques Tunica Intima - enzymology Tunica Intima - injuries Tunica Intima - pathology Vascular Endothelial Growth Factor A - metabolism Vascular Endothelial Growth Factor Receptor-1 - deficiency Vascular Endothelial Growth Factor Receptor-1 - genetics Vascular Endothelial Growth Factor Receptor-1 - metabolism Vascular Endothelial Growth Factor Receptor-2 - metabolism
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Zusammenfassung:	We have demonstrated that vascular endothelial growth factor (VEGF) expression is upregulated in injured vascular wall, and blockade of VEGF inhibited monocyte infiltration and neointima formation in several animal models. In the present study, we aimed to clarify relative role of two VEGF receptors, flt-1 versus flk-1/KDR, in neointima formation after injury using flt-1 tyrosine kinase-deficient (Flt-1 TK(-/-)) mice and soluble Flt-1(sFlt-1) gene transfer. Neointima formation was comparable between wild-type and Flt-1 TK(-/-) mice 28 days after intraluminal wire injury in femoral arteries. By contrast, neointima formation was significantly suppressed by sFlt-1 gene transfer into Flt-1 TK(-/-) mice that blocks VEGF action on flk-1 (intima/media ratio: 2.8+/-0.4 versus 1.4+/-0.4, P
ISSN:	1079-5642 1524-4636
DOI:	10.1161/atvbaha.109.183772