Unbound vascular endothelial growth factor and its receptors in breast, human milk, and newborn intestine

Background: Human milk, rich in cytokines, may contain the potent permeability- and angiogenesis-promoting agent vascular endothelial growth factor (VEGF). Objective: We wanted to study whether free or bound VEGF is present in human milk and whether it and its receptors (VEGFR-1 and -2) are expressed in lactating breast or newborn intestinal tissue. Design: The study had a longitudinal design with collection of human milk from healthy (n = 32) and diabetic (n = 5) women at 2, 7, and 30 d postpartum. Milk was analyzed for VEGF by enzyme-linked immunosorbent assay along with plasma samples collected 2 d postpartum. Immunohistochemistry was used to localize VEGF and its receptors in lactating breast and newborn intestine. Gel filtration with radiolabeled VEGF was performed to study whether human milk contains VEGF binding proteins. Results: Human milk VEGF concentrations in healthy (76 +/- 19 mug/L, (x) over bar +/- SD) and diabetic (75 +/- 25 mug/L) women did not differ at 2, 7 (23 +/- 7 and 27 +/- 8 mug/L, respectively), or 30 d (14 +/- 5 and 17 +/- 7 mug/L, respectively) postpartum. VEGF was undetectable in all but 3 plasma samples. Human milk was free of VEGF binding proteins. VEGFR-1 and -2 immunoreactivity was seen in the glandular epithelial cells of the newborn intestine and lactating breast, whereas VEGF was present only in breast glandular epithelium. Conclusions: The high concentrations of VEGF in human milk, especially colostrum, are not affected by maternal diabetes and may play a role in newborn nutrition.