Induction of vascular endothelial growth factor in balloon-injured baboon arteries: A novel role for reactive oxygen species in atherosclerosis

Johannes Ruef, Zhao Y. Hu, Li Yan Yin, Yaxu Wu, Stephen R. Hanson, Andrew B. Kelly, Laurence A. Harker, Rao Gadiparthi, Marschall S. Runge, Cam Patterson

Research output: Contribution to journalArticle

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Abstract

Neovascularization is a hallmark of neointimal formation in atherosclerotic plaques and restenotic lesions. Vascular endothelial growth factor (VEGF) promotes neovascular growth, whereas oxidative stress is a potent factor in vascular cell proliferation. To investigate the mechanisms of neovascular formation, we treated human and rat vascular smooth muscle cells (VSMCs) with H2O2. Northern blot analysis demonstrated a dose- and time-dependent increase in VEGF mRNA, with a maximum of 4-fold at 3 hours (200 μl/L). As determined by immunoblotting and enzyme-linked immunosorbent assay, VEGF protein expression and secretion were similarly increased. Human umbilical vein endothelial cells were treated with conditioned medium from VSMCs incubated with 200 μol/L H2O2. DNA synthesis, measured by thymidine incorporation, was increased 4-fold compared with control, an effect that was blocked by a neutralizing anti-VEGF antibody. The lipid peroxidation product 4-hydroxynonenal (1 μmol/L), an endogenous reactive oxygen species present in human atherosclerotic lesions, also increased VEGF secretion in VSMCs in a similar time-dependent fashion. Immunohistochemical staining and in situ hybridization of aortic sections from balloon-injured baboons demonstrated increased VEGF expression in discrete areas of the neointima and media compared with control sections, and expression correlated with the generation of 4-hydroxynonenal. Regulators of VEGF expression, such as reactive oxygen species, may enhance neovascularization of atherosclerotic and restenotic arteries.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalCirculation Research
Volume81
Issue number1
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

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Papio
Vascular Endothelial Growth Factor A
Reactive Oxygen Species
Atherosclerosis
Arteries
Vascular Smooth Muscle
Smooth Muscle Myocytes
Neointima
Human Umbilical Vein Endothelial Cells
Atherosclerotic Plaques
Conditioned Culture Medium
Immunoblotting
Northern Blotting
Thymidine
Lipid Peroxidation
In Situ Hybridization
Oxidative Stress
Enzyme-Linked Immunosorbent Assay
Cell Proliferation
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Induction of vascular endothelial growth factor in balloon-injured baboon arteries : A novel role for reactive oxygen species in atherosclerosis. / Ruef, Johannes; Hu, Zhao Y.; Yin, Li Yan; Wu, Yaxu; Hanson, Stephen R.; Kelly, Andrew B.; Harker, Laurence A.; Gadiparthi, Rao; Runge, Marschall S.; Patterson, Cam.

In: Circulation Research, Vol. 81, No. 1, 01.01.1997, p. 24-33.

Research output: Contribution to journalArticle

Ruef, Johannes ; Hu, Zhao Y. ; Yin, Li Yan ; Wu, Yaxu ; Hanson, Stephen R. ; Kelly, Andrew B. ; Harker, Laurence A. ; Gadiparthi, Rao ; Runge, Marschall S. ; Patterson, Cam. / Induction of vascular endothelial growth factor in balloon-injured baboon arteries : A novel role for reactive oxygen species in atherosclerosis. In: Circulation Research. 1997 ; Vol. 81, No. 1. pp. 24-33.
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