Dataset Information

Placental endothelial nitric oxide synthase expression and role of oxidative stress in susceptibility to preeclampsia in Pakistani women.

ABSTRACT:

Background

Preeclampsia (PE): a hypertensive disorder of pregnancy characterized by de novo development of concurrent hypertension and proteinuria. The prevailing theory determined that PE starts from the placenta and ends in the maternal endothelium. Role of endothelial dysfunction in the onset of PE has been reported in different populations. Therefore, present study was designed to investigate the localization and expression of endothelial nitric oxide synthase (eNOS) and role of oxidative stress markers in preeclamptic Pakistani women.

Methods

A total of 400 blood samples (PE = 200, controls = 200) and 100 placental tissues (PE = 50, controls = 50) were recruited from pregnant women. Reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (POD) levels were analyzed through spectrophotometer. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) were carried out to estimate the localization and expression of eNOS in the placentas of PE patients and healthy pregnant women.

Results

Significantly increased levels of POD (0.01), TBARS (0.04), and ROS (p ? .001) were determined in preeclamptic women while, nonsignificant change in SOD and CAT was observed in both groups. Reduced eNOS immunoreactivity (p ? .001) and mRNA abundance (p ? .001) was observed in preeclamptic group as compared to control group.

Conclusion

Considering the results of current study, it is concluded that decreased eNOS expression and oxidative stress could play a role in the pathology of PE seen both in placenta and ultimately in maternal endothelium. However, large studies are necessary to validate these findings to prevent maternal and neonatal morbidity and mortality in Pakistani population.

SUBMITTER: Shaheen G

PROVIDER: S-EPMC6978247 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Placental endothelial nitric oxide synthase expression and role of oxidative stress in susceptibility to preeclampsia in Pakistani women.

Shaheen Ghazala G Jahan Sarwat S Ain Qurat Ul QU Ullah Asad A Afsar Tayyaba T Almajwal Ali A Alam Iftikhar I Razak Suhail S

Molecular genetics & genomic medicine 20191108 1

<h4>Background</h4>Preeclampsia (PE): a hypertensive disorder of pregnancy characterized by de novo development of concurrent hypertension and proteinuria. The prevailing theory determined that PE starts from the placenta and ends in the maternal endothelium. Role of endothelial dysfunction in the onset of PE has been reported in different populations. Therefore, present study was designed to investigate the localization and expression of endothelial nitric oxide synthase (eNOS) and role of oxid ...[more]

PMID: 31701677

Similar Datasets

Project description:Decreased nitric oxide (NO) bioavailability plays a critical role in the pathophysiology of preeclampsia (PE). Recent evidence indicates that S-glutathionylation may occur on the endothelial nitric oxide synthase (eNOS), leading to eNOS uncoupling, characterized by a decreased NO production and an increased generation of superoxide anion (O2•-). We hypothesized that eNOS glutathionylation may occur in PE placentas and participate in eNOS dysfunction. The glutathionylation of eNOS was investigated in thirteen PE-affected patients and in nine normal pregnancies. Immunofluorescence, confocal microscopy and western-blot experiments carried out on eNOS immunoprecipitates, revealed a high level of eNOS glutathionylation in PE placentas, mostly reversed by dithiotreitol (DTT), thus indicative of S-glutathionylation. In order to investigate whether eNOS glutathionylation may alter trophoblast migration, an important event occurring during early placentation, cultured HTR-8/SVneo human trophoblasts (HTR8) were exposed either to low pO2 (O2 1%) or to pO2 changes (O2 1-20%), in order to generate oxidative stress. Trophoblasts exposed to low pO2, did not undergo oxidative stress nor eNOS S-glutathionylation, and were able to generate NO and migrate in a wound closure model. In contrast, trophoblasts submitted to low/high pO2 changes, exhibited oxidative stress and a (DTT reversible) S-glutathionylation of eNOS, associated with reduced NO production and migration. The autonomous production of NO seemed necessary for the migratory potential of HTR8, as suggested by the inhibitory effect of eNOS silencing by small interfering RNAs, and the eNOS inhibitor L-NAME, in low pO2 conditions. Finally, the addition of the NO donor, NOC-18 (5 µM), restored in part the migration of HTR8, thereby emphasizing the role of NO in trophoblast homeostasis. In conclusion, the high level of eNOS S-glutathionylation in PE placentas provides new insights in the mechanism of eNOS dysfunction in this disease.

Dataset Information

Placental endothelial nitric oxide synthase expression and role of oxidative stress in susceptibility to preeclampsia in Pakistani women.

Background

Methods

Results

Conclusion

Publications

Placental endothelial nitric oxide synthase expression and role of oxidative stress in susceptibility to preeclampsia in Pakistani women.

Similar Datasets

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