TY - JOUR
T1 - Essential role of vascular endothelial growth factor and Flt-1 signals in neointimal formation after periadventitial injury
AU - Zhao, Qingwei
AU - Egashira, Kensuke
AU - Hiasa, Ken Ichi
AU - Ishibashi, Minako
AU - Inoue, Shuujirou
AU - ohtani, kisho
AU - Tan, Chunyan
AU - Shibuya, Masabumi
AU - Takeshita, Akira
AU - Sunagawa, Kenji
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
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U2 - 10.1161/01.ATV.0000147161.42956.80
DO - 10.1161/01.ATV.0000147161.42956.80
M3 - Article
C2 - 15472126
AN - SCOPUS:20844461824
VL - 24
SP - 2284
EP - 2289
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 12
ER -