Apoptotic and stress signaling markers are augmented in preeclamptic placenta and umbilical cord

Syeda H Afroze,Ram R Kalagiri,Michelle Reyes,Jacqueline D Zimmerman,Madhava R Beeram,Nathan Drever,David C Zawieja,Thomas J Kuehl,Mohammad N Uddin

doi:10.1016/j.bbacli.2016.05.003

Syeda H Afroze, Ram R Kalagiri + Show 7 more

Open Access

https://doi.org/10.1016/j.bbacli.2016.05.003

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Abstract

ObjectivePreeclampsia (preE) has a significant link to alterations of placental function leading to stress and apoptotic signaling, which pass the placental barrier and leave persistent defect in the circulation of the offspring. We assessed apoptotic signaling in placentas and umbilical cords from patients with and without preE. MethodsWe collected placental and cord tissues from 27 normal pregnant (NP) women and 20 preE consenting patients after delivery in an IRB approved prospective study. p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-apoptotic Bcl-2-associated X (Bax), anti-apoptotic Bcl-2, caspase-9, and pro-inflammatory cyclooxygenase-2 (Cox-2) were evaluated by western blot and immunohistochemistry. Comparisons were performed using Student's t-test. Resultsp38 phosphorylation (Placenta: 1.5 fold, Cord: 1.7 fold), ratio of Bax/Bcl-2 (Placenta: 1.7 fold, Cord: 2.2 fold), caspase-9 (Placenta: 1.5 fold, Cord: 1.8 fold) and Cox-2 (Placenta: 2.5 fold, Cord: 2.3 fold) were up-regulated (p<0.05) in preE compared to NP patients. Average hospital stays for preE babies were longer than NP babies. No complications were reported for NP babies; however, all of preE babies had multiple complications. ConclusionsApoptotic and stress signaling are augmented in preE placenta and cord tissue that alter the intrauterine environment and activates the detrimental signaling that is transported to fetus.

Highlights

Preeclampsia, is a clinical syndrome characterized by a systolic blood pressure (BP) of ≥140 mm Hg or a diastolic BP of ≥90 mm Hg accompanied by proteinuria of ≥0.3 g in a 24-hour urine sample that begins after 20 weeks gestation [1,2,3,4]
The apoptotic and stress signaling proteins were significantly upregulated in preE placentas and umbilical cords compared to normal pregnancies
The proposed mechanisms of reduced uterine perfusion and hypoxia, elevated antiangiogenic factors and systemic endothelial dysfunction are the significant pathophysiologic mechanism leading to the development of preE, and the higher BPs lead to increased stroke and atherogenesis [4,20,21]

Summary

Introduction

Preeclampsia (preE), is a clinical syndrome characterized by a systolic blood pressure (BP) of ≥140 mm Hg or a diastolic BP of ≥90 mm Hg accompanied by proteinuria of ≥0.3 g in a 24-hour urine sample that begins after 20 weeks gestation [1,2,3,4]. Theories proposed to cause preeclampsia include angiogenic imbalance [2,5,6], autoantibodies to angiotensin type 1 (AT1) receptor [7,8], cardiotonic steroids [9,10,11], genetic predisposition [3] and immunological factors [12]. The angiogenic imbalance is the effect of vascular endothelial growth factor (VEGF) on the proliferation and survival of endothelial cells. It has a vasodilator effect on the systemic vessels that increases vascular permeability [2,3,5,12]. MBG plays a major role in the pathogenesis of preE including activation of apoptotic signaling and alteration of endothelial cell growth [3,11,14]

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