Essential role of vascular endothelial growth factor and Flt-1 signals in neointimal formation after periadventitial injury

Qingwei Zhao, Kensuke Egashira, Hiasa Ken-Ichi, Minako Ishibashi, Shuujirou Inoue, kisho ohtani, Chunyan Tan, Masabumi Shibuya, Akira Takeshita, Kenji Sunagawa

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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.

Original languageEnglish
Pages (from-to)2284-2289
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number12
DOIs
Publication statusPublished - Dec 1 2004

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Vascular Endothelial Growth Factor A
Wounds and Injuries
Inflammation
Vascular Endothelial Growth Factor Receptor
Chemokine CCL2
Genes
Transfection
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Cytokines
Lipids

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Essential role of vascular endothelial growth factor and Flt-1 signals in neointimal formation after periadventitial injury. / Zhao, Qingwei; Egashira, Kensuke; Ken-Ichi, Hiasa; Ishibashi, Minako; Inoue, Shuujirou; ohtani, kisho; Tan, Chunyan; Shibuya, Masabumi; Takeshita, Akira; Sunagawa, Kenji.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 24, No. 12, 01.12.2004, p. 2284-2289.

Research output: Contribution to journalArticle

Zhao, Qingwei ; Egashira, Kensuke ; Ken-Ichi, Hiasa ; Ishibashi, Minako ; Inoue, Shuujirou ; ohtani, kisho ; Tan, Chunyan ; Shibuya, Masabumi ; Takeshita, Akira ; Sunagawa, Kenji. / Essential role of vascular endothelial growth factor and Flt-1 signals in neointimal formation after periadventitial injury. In: Arteriosclerosis, thrombosis, and vascular biology. 2004 ; Vol. 24, No. 12. pp. 2284-2289.
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AU - Takeshita, Akira

AU - Sunagawa, Kenji

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