PDGF(BB) increases myocardial production of VEGF: shift in VEGF mRNA splice variants after direct injection of bFGF, PDGF(BB), and PDGF(AB)

J Surg Res. 2002 Oct;107(2):203-9. doi: 10.1006/jsre.2002.6510.

Abstract

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis. We hypothesized that a combination of recombinant angiogenic proteins might induce myocardial VEGF production and cause a shift in the mRNA signal produced.

Materials and methods: The left ventricles of New Zealand white rabbits were injected with 500 microL of saline, basic fibroblast growth factor (bFGF), platelet-derived growth factor-AB (PDGF(AB)), platelet-derived growth factor-BB (PDGF(BB)), bFGF + PDGF(AB), or bFGF + PDGF(BB). Myocardial VEGF production was analyzed by ELISA while mRNA splice variants were analyzed by RT-PCR 3 and 7 days after injection.

Results: PDGF(BB) alone caused the most pronounced induction of VEGF. Three days after injection the induction of VEGF by PDGF(BB) was significant compared to all treatment groups, except the bFGF + PDGF(BB) group. Induction of VEGF by PDGF(BB) was associated with a decrease in mRNA production of VEGF(121) within the myocardium.

Conclusions: Injection of PDGF(BB) induces significant production of VEGF within the myocardium. This induction of VEGF production is associated with a shift toward other, less soluble forms of VEGF. These findings may allow more precise regulation of the myocardial response to therapeutic angiogenesis.

MeSH terms

  • Animals
  • Becaplermin
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblast Growth Factor 2 / pharmacology*
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Lymphokines / biosynthesis*
  • Lymphokines / genetics
  • Myocardium / metabolism*
  • Platelet-Derived Growth Factor / pharmacology*
  • Proto-Oncogene Proteins c-sis
  • RNA Splicing*
  • Rabbits
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • platelet-derived growth factor AB
  • Fibroblast Growth Factor 2
  • Becaplermin