LGA-newborn from patients with pregestational obesity present reduced adiponectin-mediated vascular relaxation and endothelial dysfunction in fetoplacental arteries

Abstract

Maternal obesity is associated with large-for-gestational-age (LGA) neonates and programming of obesity-related cardiovascular disease in the offspring, however, the mechanisms that lead to the later are unclear. Presently, interpretations of NO-dependent changes in vascular function in LGA newborn from obese mothers are conflicting. Adiponectin improves endothelial function by increasing eNOS activity and NO production. We propose that LGAs from obese mothers present a diminished vascular response to adiponectin; thus, affecting eNOS and AMPK activation. Chorionic arteries, umbilical cord and primary cultures of umbilical artery endothelial cells (HUAEC) were collected at term (>38 wks) from uncomplicated singleton pregnancies of LGA and adequate-for-gestational (AGA) newborn. Vascular reactivity of chorionic plate arteries was assessed by wire myography. mRNA expression of adiponectin receptors 1 (AdipoR1) and AdipoR2 in HUAEC was determined by qPCR. Protein expression of AdipoR1, AdipoR2, AMPK, phospho-AMPKα^Thr172, eNOS and phospho-eNOS^Ser1177 after stimulation with AdipoRon was determined by Western Blot. Maximal adiponectin-induced chorionic artery relaxation in LGAs was diminished compared to control. In vitro studies showed no differences in expression of AdipoRs, total AMPK and, eNOS activation between groups; however, higher expression of total eNOS and AMPK activation in HUAEC of LGA relative to AGAs were observed. LGA HUAEC showed diminished NO production and eNOS activity compared to AGA in response to AdipoRon but no changes in AMPK activation. Placental endothelium of LGAs shows a diminished vascular response to adiponectin. Moreover, eNOS activation and adiponectin-dependent NO production is lower in HUAEC of LGA from obese mothers, indicating they present dysfuncional placental-endothelial responses. This article is protected by copyright. All rights reserved

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