Abstract 1884 Poster Session IV, Tuesday, 5/4 (poster 304)

Objective: Angiogenesis and development of the fetal pulmonary circulation parallels the growth and development of the fetal lung. Vascular endothelial growth factor (VEGF) stimulates angiogenesis and is believed to have a vital role in the development of blood vessels, but little is known about its role in the development of the fetal lung, a highly vascular organ. VEGF binds to tyrosine kinase receptors (VEGFR-1/Flt and VEGFR-2/Flk) to stimulate angiogenesis, and these receptors are found in fetal lung tissue. We hypothesized that increased pulmonary vascular development as the fetal lung grows is dependent on increases in mRNA expression of VEGF and mRNA expression of one of its receptors, VEGFR-2/Flk during a period of rapid growth of the fetal lung and greatly increased pulmonary vascular development at the end of gestation in the fetal rat.

Methods: We harvested lungs from fetal rat pups on day 19 (n=10) or day 21 (n=7), term = 21.5 days, and performed RT-PCR on mRNA using primers for VEGF and its receptor, VEGFR-2/Flk, normalized to β actin mRNA levels and converted to densitometric units. The data are mean ± sem and were compared by unpaired t-tests between the time periods.

Results: (Table) During this two day period, the fetal lungs almost doubled in size. As anticipated, we found a significant 5-fold increase in VEGF mRNA expression during this period of increased vascularity of the lung. In contrast, we found a significant decrease in VEGFR-2/Flk receptor mRNA expression during this same period.

Table 1 No caption available
Full size table

Conclusion: We speculate that the known increase in pulmonary vascularity at the end of gestation is stimulated by increased VEGF expression and is important for development of the fetal lung during this greatly increased growth. It appears that fetal vascular development may not be dependent on increased VEGFR-2/Flk receptor expression. It may be that receptor turnover is altered at the end of gestation or that another receptor for VEGF, namely VEGFR-1/Flt, is more important at the end of gestation in fetal pulmonary vascular development.