Vascular endothelial growth factor is necessary in the development of arteriosclerosis by recruiting/activating monocytes in a rat model of long-term inhibition of nitric oxide synthesis

Qingwei Zhao, Kensuke Egashira, Shujiro Inoue, Makoto Usui, Shiro Kitamoto, Weihua Ni, Minako Ishibashi, Ken Ichi Hiasa, Toshihiro Ichiki, Masabumi Shibuya, Akira Takeshita

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Abstract

Background - It remains unclear whether vascular endothelial growth factor (VEGF) is a proarteriosclerotic or an antiarteriosclerotic factor. We recently reported that long-term inhibition of nitric oxide by administering Nω-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular inflammation and arteriosclerosis. Methods and Results - We used this animal model to investigate the role of VEGF in arteriosclerosis. We blocked VEGF activity in vivo by transfecting with plasmid DNA encoding the murine soluble FLT-1 (sFLT-1) gene into thigh muscle. Soluble FLT-1 can suppress VEGF activity both by sequestering VEGF and by functioning as a dominant-negative inhibitor of VEGF receptors. We observed vascular inflammation associated with increased VEGF expression within 3 days of L-NAME administration, which was prevented by pretreatment with ACE inhibitor, angiotensin II receptor antagonist, or neutralizing monocyte chemoattractant protein-1 antibody. The sFLT-1 gene transfer attenuated the early vascular inflammation and prevented late arteriosclerosis. The sFLT-1 gene transfer also inhibited increased expression of monocyte chemoattractant protein-1 and transforming growth factor-β, indicating creation of a positive feedback loop to cause arteriosclerosis. Conclusions - VEGF is necessary in the development of arteriosclerosis by mediating monocyte recruitment and activation in this model.

Original languageEnglish
Pages (from-to)1110-1115
Number of pages6
JournalCirculation
Volume105
Issue number9
DOIs
Publication statusPublished - Mar 5 2002

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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