PDGF_BB increases myocardial production of VEGF: Shift in VEGF mRNA splice variants after direct injection of bFGF, PDGF_BB, and PDGF_AB

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 VEGF₁₂₁ 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.