Mature Twin Neonates Exhibit Oxidative Stress via Nitric Oxide Synthase Dysfunctionality: A Prognostic Stress Marker in the Red Blood Cells and Umbilical Cord Vessels.

Payal Chakraborty,Krisztina N Dugmonits,Edit Hermesz,Hajnalka Orvos

doi:10.3390/antiox9090845

Payal Chakraborty, Krisztina N Dugmonits + Show 2 more

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https://doi.org/10.3390/antiox9090845

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Journal: Antioxidants (Basel, Switzerland)	Publication Date: Sep 10, 2020
Citations: 4	License type: CC BY 4.0

Affiliation: University of Szeged

Abstract

Intrauterine hypoxic condition increases the generation of reactive oxygen species and fetal oxidative stress. Multiple pregnancy always bears an additional oxidative stress condition with severe complications, such as prematurity, structural abnormalities, delayed development and low birthweight. The umbilical cord (UC) vessels, along with circulating fetal red blood cells (RBCs), highly determine the oxygenation status of fetus and regulate the feto-placental circulation. As UC lacks innervation, the activation of the endothelial nitric oxide synthase (NOS3) is fundamental for proper NO production. Therefore, we aimed to study the NOS3 activation pathways along with damages to macromolecules in the endothelium of UC vessels and RBCs of mature non-discordant twins, in connection to major differences in their birth weight. We provide evidence that, under severe hypoxic conditions such as twin pregnancy, the NOS3-related NO production pathways are altered both in UC vessels and RBCs; moreover, the extent of changes is highly birthweight-specific. Furthermore, macromolecular damages are prominent in the RBCs and arteries compared to the vein, with a similar increase in the Arginase1 level, which is believed to play a role in NOS3 functionality, resulting in endothelial dysfunctionality, which might have relevance to the major etiologies of cardiovascular diseases in later life.

Highlights

Increasing evidence suggests that enhanced oxidative insults during intrauterine development frequently contribute to the occurrence of pathological conditions in post-natal or adult life [1,2].With considerable alterations in the physiological and metabolic functions, the delicate balance between reactive oxygen species (ROS), and the intrinsic antioxidant defense system is disrupted
The NOS3 and the pSer1177 NOS3 levels were significantly lower in the endothelium of both the arteries and veins, originated from Hwt, as compared to the age and weight matched controls
Based on the data by Pernow et al [23,24], in the present study we looked for a cross-talk between circulating red blood cells (RBCs) and vascular endothelium and focused on the detailed molecular mechanism of nitric oxide (NO) production limited to the RBC population, and in the umbilical cord (UC) endothelium

Summary

Introduction

Increasing evidence suggests that enhanced oxidative insults during intrauterine development frequently contribute to the occurrence of pathological conditions in post-natal or adult life [1,2].With considerable alterations in the physiological and metabolic functions, the delicate balance between reactive oxygen species (ROS), and the intrinsic antioxidant defense system is disrupted. Antioxidants 2020, 9, 845 placental or umbilical cord disorders, such as intrauterine hypoxia and an impaired blood flow to the fetus [8,9,10]. The subcellular localization of NOS3 and its activation pathway are tightly controlled by major factors such as the substrate L-arginine concentration, availability of co-factors, rate of electron transfer, post-translational modifications and diverse interacting proteins. These factors can be highly affected by excessive ROS production with low endogenous antioxidant capacity possibly influenced by intrinsic or extrinsic pathophysiological factors, leading to oxidative stress conditions [13]

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