Basic fibroblast growth factor and epithelial growth factor induce secretion of vascular endothelial growth factor by human aortic smooth muscle cells but not endothelial cells

Funmilayo Belgore, Gregory Lip, Andrew Blann

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background Endothelial cell dysfunction and smooth muscle cell (SMC) proliferation are major events in atherogenesis. Both cells are a source of growth factors that mediate cellular proliferation and chemotaxis. Inappropriate production of, and/or response to, these growth factors ( such as vascular endothelial growth factor, VEGF, and basic fibroblast growth factor ( bFGF)) may contribute to atherogenesis and therefore to disease progression. Methods Production of VEGF and its soluble receptor (sFlt-1) by human SMCs and human umbilical endothelial cells ( HUVECs) after stimulation with bFGF were examined by ELISA of cell culture media and by Western blotting. Results Smooth muscle cells produced significantly more VEGF than HUVECs ( P <0.05) after 24 h of culture with bFGF levels &GE; 0.001 μg mL(-1). bFGF induced dose-dependent production of VEGF by SMCs, where maximum production was present in 1 μg mL(-1) of bFGF. Conversely, the SMCs produced less sFlt-1 than HUVECs (P <0.05). However, bFGF induced dose-dependent phosphorylation of Flt1 and another VEGF receptor, KDR, in HUVECs but not SMCs. There was no VEGF or sFLT-1 after 6 h of culture in any dose of bFGF in either type of cell. Conclusions Differences in the production of VEGF and sFlt-1 by SMCs and HUVECs are consistent with the role of these cells in angiogenesis. Induction of VEGF production and expression by bFGF in these cells indicates that this growth factor may participate in angiogenesis indirectly by the induction of VEGF. The production of sFlt-1 by both cell types is in agreement with the notion that sFlt-1 may be involved in the regulation of VEGF activity. Additionally, the ability of bFGF to induce dose-dependent phosphorylation of KDR in HUVECs highlights the important role of bFGF in VEGF-mediated angiogenic processes.
Original languageEnglish
Pages (from-to)833-839
Number of pages7
JournalEuropean journal of clinical investigation
Volume33
Issue number10
DOIs
Publication statusPublished - 1 Oct 2003

Keywords

  • endothelial cells
  • smooth muscle cells
  • bFGF
  • VEGF

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