PDGFBB Increases Myocardial Production of VEGF: Shift in VEGF mRNA Splice Variants after Direct Injection of bFGF, PDGFBB, and PDGFAB

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 μL 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.

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