174 Expression of Angiopoietin-2 and Endostatin in Intrauterine Growth Restriction During The Perinatal Period

Abstract

Background: Angiopoietin-2 (Ang2) is an endothelial cell-specific growth factor, which acts by blocking stabilization and maturation of vessels allowing them to remain in a more plastic state and respond to sprouting signals provided by other angiogenic factors. Ang2 gene expression is up-regulated by hypoxia, present in intrauterine growth restriction (IUGR) pregnancies. On the contrary, hypoxia down-regulates production of endostatin (End), a potent angiostatic factor derived from collagen XVIII. This study aimed at investigating circulating Ang2 and End levels in maternal blood (MS) during the first stage of labor, in the doubly clamped umbilical cord (UC) at delivery, representing fetal state and in the neonate in the first (N1) and fourth (N4) day of life, reflecting transition and stabilization to extrauterine life, respectively

Methods: Ang2 and End were determined by enzyme immunoassay methods in serum, deriving from 20 fullterm appropriate for gestational age (AGA) and 40 fullterm IUGR infants, as well as from their mothers.

Results: Statistical significant difference was noted in N4 Ang2, being higher in IUGR (p=0.030), (while in N1 Ang2 was only indicative-p=0.057) and in UC End, being lower in IUGR (p=0.002), as compared to AGA cases. Statistical significant correlations existed for Ang2 between: MS and UC, N1, N4 (p=0.000, p=0.001, p=0.017 respectively), UC and N1, N4 (p=0.000, p=0.000 respectively), N1 and N4 (p=0.000) and for End between N1 and N4 (p=0.006). In the IUGR group variables presenting a statistically significant association with: a) MS Ang2, were gestational age (p=0.011), placental weight (p=0.013), gender (p=0.002) and birth length (p=0.023), b) UC Ang2, was gestational age (p=0.042), c) N1 Ang2, were gestational age (p=0.000) and birth weight (p=0.003) d) N4 Ang2, were gestational age (p=0.000) and birth weight (p=0.023), e) MS End, were gender (p=0.003), gestational age (p=0.007) and birth length (p=0.006), f) UC End, were placental weight (p=0.038) and gender (p=0.031), g) N1 End, was gender (p=0.050).

Conclusion: High neonatal Ang2 and low fetal End is documented in IUGR infants, possibly due to intrauterine action of hypoxia on these factors. In IUGR fetuses End is associated with placental weight. Similarly, Ang2 in IUGR fetuses is associated with gestational age and in IUGR neonates with gestational age and birth weight, in general indicating the impact of these factors on angiogenesis and tissue growth.

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