Immunoexpression of GADD45β in the myocardium of newborns experiencing perinatal hypoxia

Abstract

Aim: Among the several organs affected by perinatal hypoxia, the heart plays a central role, with cell death caused mainly by apoptosis. One of the biomarkers most often linked to hypoxia-derived apoptosis of cardiomyocytes in animals is Gadd45β. From the published literature, Gadd45β is proposed as a biomarker of hypoxia-induced lesion in cardiomyocytes, both in vitro, as well as in animal models. Our study suggests that this protein can be used as an early biomarker of cell damage in neonate's cardiomyocytes (humans specimens), a process that can ultimately lead to apoptosis. The aim is to determine levels of tissue immunoexpression of the Gadd45β biomarker in myocardium samples of newborns affected by hypoxia, and to correlate these results with clinical and anatomopathologic data.

Methods: Myocardium samples from the left ventricle of newborns were used. The samples were collected from 78 autopsies performed in neonates of both genders, with hypoxia (Apgar score at five minutes below 6 and/or pH below 7.2 and/or autopsy with anatomopathological signs of hypoxia), who had died within the first day of life. All samples were organized in Tissue Microarray. Immunohistochemistry analysis, using anti-Gadd45β as the primary antibody, was performed on 3 multi-sample histological slides. There was no correlation between Gadd45β tissue immunoexpression and neonatal weight (p=0.93), gestational age (p=0.16), Apgar score at first minute (p=0.914), Apgar score at five minutes (p=0.988) and arterial blood pH (p=0.542). There was a relation between Gadd45β tissue immunoexpression and survival (p=0.02). The maximum peak of Gadd45β tissue immunoexpression was 8.43% HPF (high power field) and was observed around of six hours of life.

Conclusion: Gadd45β could be a suitable biomarker of cardiomyocytes apoptosis in newborns experiencing hypoxia in the first day of life, as its highest tissue immunoexpression around at the first six hours after birth.

Keywords: Apoptosis; Hypoxia; Immunohistochemistry; Newborn.