Hepatocyte growth factor suppresses vascular endothelial growth factor-induced expression of endothelial ICAM-1 and VCAM-1 by inhibiting the nuclear factor-κB pathway

Jeong Ki Min, Young Mi Lee, Hun Kim Jeong, Young Myeong Kim, Wan Kim Sung, Soo Young Lee, Song Gho Yong, Taeg Oh Goo, Young-Guen Kwon

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are potent angiogenic factors that have been used clinically to induce angiogenesis. However, concerns have been raised about VEGF because of its proinflammatory actions, which include enhancing the adhesion of leukocytes to endothelial cells. We have examined the possible antiinflammatory effects of HGF on the vasculature. HGF, unlike VEGF, did not alter leukocyte adhesion to endothelial cells. Instead it inhibited VEGF-induced leukocyte-endothelial cell interactions and the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In a skin inflammation model, VEGF-treated mice showed a significant increase of leukocytes infiltrated or adherent to the luminal surface of blood vessels, as compared with vehicle- or HGF-treated mice. The VEGF effect was markedly suppressed by coadministration of HGF. RT-PCR and promoter analysis revealed that HGF downregulated VEGF-mediated expression of ICAM-1 and VCAM-1 at the transcriptional level. Furthermore, these inhibitory effects coincided with suppression of IκB kinase activity, and this in turn prevented the activation of the inflammatory transcription factor NF-κB. Taken together, our results demonstrate that HGF suppresses VEGF-induced inflammation presumably by inhibiting the endothelial NF-κB pathway. This suggests that combined treatment with HGF and VEGF could be superior to treatment with either factor alone for enhancing therapeutic angiogenesis while avoiding inflammation.

Original languageEnglish
Pages (from-to)300-307
Number of pages8
JournalCirculation Research
Volume96
Issue number3
DOIs
Publication statusPublished - 2005 Feb 18

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Hepatocyte Growth Factor
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Vascular Endothelial Growth Factor A
Leukocytes
Endothelial Cells
Inflammation
Angiogenesis Inducing Agents
Cell Communication
Blood Vessels
Anti-Inflammatory Agents
Transcription Factors
Phosphotransferases
Down-Regulation
Polymerase Chain Reaction
Skin

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Min, Jeong Ki ; Lee, Young Mi ; Jeong, Hun Kim ; Kim, Young Myeong ; Sung, Wan Kim ; Lee, Soo Young ; Yong, Song Gho ; Goo, Taeg Oh ; Kwon, Young-Guen. / Hepatocyte growth factor suppresses vascular endothelial growth factor-induced expression of endothelial ICAM-1 and VCAM-1 by inhibiting the nuclear factor-κB pathway. In: Circulation Research. 2005 ; Vol. 96, No. 3. pp. 300-307.
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Hepatocyte growth factor suppresses vascular endothelial growth factor-induced expression of endothelial ICAM-1 and VCAM-1 by inhibiting the nuclear factor-κB pathway. / Min, Jeong Ki; Lee, Young Mi; Jeong, Hun Kim; Kim, Young Myeong; Sung, Wan Kim; Lee, Soo Young; Yong, Song Gho; Goo, Taeg Oh; Kwon, Young-Guen.

In: Circulation Research, Vol. 96, No. 3, 18.02.2005, p. 300-307.

Research output: Contribution to journalArticle

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AU - Min, Jeong Ki

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