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

Qingwei Zhao, Kensuke Egashira, Ken Ichi Hiasa, Minako Ishibashi, Shujiro Inoue, Kisho Ohtani, Chunyan Tan, Masabumi Shibuya, Akira Takeshita, Kenji Sunagawa

Research output: Contribution to journalArticle

69 Citations (Scopus)

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

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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