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 permeabil ity- and angiogenesis-promoting agent vascular endothelial growth factor (V EGF). Objective: We wanted to study whether free or bound VEGF is present in huma n milk and whether it and its receptors (VEGFR-1 and -2) are expressed in l actating breast or newborn intestinal tissue. Design: The study had a longitudinal design with collection of human milk f rom healthy (n = 32) and diabetic (n = 5) women at 2, 7, and 30 d postpartu m. Milk was analyzed for VEGF by enzyme-linked immunosorbent assay along wi th plasma samples collected 2 d postpartum. Immunohistochemistry was used t o localize VEGF and its receptors in lactating breast and newborn intestine . Gel filtration with radiolabeled VEGF was performed to study whether huma n milk contains VEGF binding proteins. Results: Human milk VEGF concentrations in healthy (76 +/- 19 mug/L, (x) ov er 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 immu noreactivity was seen in the glandular epithelial cells of the newborn inte stine and lactating breast, whereas VEGF was present only in breast glandul ar epithelium. Conclusions: The high concentrations of VEGF in human milk, especially colo strum, are not affected by maternal diabetes and may play a role in newborn nutrition.