MODULATION OF THE PLACENTAL HDL AND LDL CHOLESTEROL UPTAKE BY THE MATERNAL LIPIDS LEVEL IN HUMAN TROPHOBLAST

Abstract

Pregnancy associates with increased maternal level of lipids (i.e., maternal physiological dyslipidaemia, MPD). However, when lipid level reaches over the physiological values, maternal supraphysiological dyslipidaemia (MSPD) is recognized. The consequences of MSPD in the foetus include foetoplacental endothelial dysfunction and increased foetal atherosclerosis. Gestational diabetes mellitus (GDM) associates with MSPD and endothelial dysfunction in umbilical veins, the latter caused mainly by maternal hyperglycaemia and hyperinsulinemia. However, the consequences of MSPD in GDM pregnancies in the foetal vasculature have been neglected.Objectives: To determine whether MSPD alters endothelial-dependent umbilical vein reactivity in GDM pregnancies.Methods: Placentas were collected at Hospital Clínico UC-CHRISTUS (Santiago de Chile). Umbilical veins rings were isolated from four study groups: GDM or normal pregnancies, with or without MSPD. Vein rings were mounted in a wire myograph and the response to insulin (0.1-1000 nmol/L, 5 min) or calcitonin-gene related peptide (CGRP, 0.01-100 nmol/L, 5 min) in KCl-preconstricted vessels (32 mmol/L) was measured. Nitric oxide (NO)-dependent dilation was estimated in the absence or presence of the NO synthase inhibitor NG-nitro-L-arginine methyl-ester (L-NAME, 100 μmol/L, 20 min).Results: GDM showed lower (P<0.05, n = 5-10) NO-dependent maximal relaxation (Rmax) in response to insulin (GDM: 17 ± 2%, normal: 43 ± 6%) and CGRP (GDM: 15 ± 3%, normal: 30 ± 3%). CGRP-dilation was further reduced in vein rings from GDM with MSPD (MSPD: 12 ± 1%) and in normal pregnancies with MSPD (MSPD: 14 ± 1%), but not in response to insulin. Conclusion: MSPD contributes to GDM-associated endothelial dysfunction by worsening the vascular dilation of umbilical vein rings in this pathology.Funding: FONDECYT 1150344/1150377, BF holds Faculty of Medicine, PUC-PhD fellowship.