Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis.

• Authors: Hideo Kimura , Hiroyasu Esumi
• Languages of publication: EN

Abstracts

EN

Physiologically, angiogenesis is tightly regulated, or otherwise it leads to pathological processes, such as tumors, inflammatory diseases, gynecological diseases and diabetic retinopathy. The vascular endothelial growth factor (VEGF) is a potent and critical inducer of angiogenesis. The VEGF gene expression is regulated by a variety of stimuli. Hypoxia is one of the most potent inducers of the VEGF expression. The hypoxia inducible factor 1 (HIF-1) plays as a key transcription factor in hypoxia-mediated VEGF gene upregulation. Nitric oxide (NO) as well as hypoxia is reported to upregulate the VEGF gene by enhancing HIF-1 activity. The Akt/protein kinase B (PKB) pathway may be involved in NO-mediated HIF-1 activation in limited cell lines. There are some reports of negative effects of NO on HIF-1 and VEGF activity. These conflicting data of NO effects may be attributed mainly to the amount of released NO. Indeed, NO can be a positive or negative modulator of the VEGF gene under the same conditions simply by changing its amounts. The VEGF-mediated angiogenesis requires NO production from activated endothelial NO synthase (eNOS). Activation of eNOS by VEGF involves several pathways including Akt/PKB, Ca2+/calmodulin, and protein kinase C. The NO-mediated VEGF expression can be regulated by HIF-1 and heme oxygenase 1 (HO-1) activity, and the VEGF-mediated NO production by eNOS can be also modulated by HIF-1 and HO-1 activity, depending upon the amount of produced NO. These reciprocal relations between NO and VEGF may contribute to regulated angiogenesis in normal tissues.

Keywords

EN

angiogenesis; vascular endothelial growth factor; hypoxia inducible factor 1; hypoxia; reciprocal regulation; nitric oxide

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2003
• Volume: 50
• Issue: 1
• Pages: 49-59

Dates

published

2003

received

2003-01-02

accepted

2003-03-04

Contributors

author

Hideo Kimura

• Investigative Treatment Division, National Cancer Center Research Institute East, Chiba, Japan

author

Hiroyasu Esumi

• Investigative Treatment Division, National Cancer Center Research Institute East, Chiba, Japan

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