scholarly journals Association of endothelial nitric oxide synthase gene variants with preeclampsia

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ghazala Shaheen ◽  
Sarwat Jahan ◽  
Nousheen Bibi ◽  
Asmat Ullah ◽  
Rani Faryal ◽  
...  

Abstract Background Preeclampsia (PE) is a complex pregnancy hypertensive disorder with multifaceted etiology. The endothelial nitric oxide synthase (eNOS) gene and nitric oxide (NO) levels has been reported to be associated with PE predisposition in various populations. Therefore, present study was designed to investigate the role of NO levels and eNOS gene variants in preeclamptic women in Pakistan. Methods A total of 600 women were evaluated, 188 of PE with mild features, 112 of PE with severe features and 300 normotensive pregnant women. NO levels were detected by Greiss reaction method and genotyping following sequencing was conducted for eNOS gene variants. Further insilico studies were performed to get insights into the structural and functional impact of identifies mutation on eNOS protein as well as on protein regulation. Results Reduced concentrations of NO were reported in all PE groups (p < 0.05) as compared to controls. The frequency of c.894 T (p.298Asp) and g.-786C alleles were significantly associated with PE. In addition, novel homozygous variant g.2051G > A was also significantly associated with PE when compared to normotensive women. Dynamic simulation studies revealed that Glu298Asp mutation destabilize the protein molecule and decrease the overall stability of eNOS protein. Molecular docking analysis of mutant promoter with transcription factors STAT3 and STAT6 proposed changes in protein regulation upon these reported mutations in upstream region of the gene. Conclusion Considering the results of current study, the functional alterations induced by these variants may influence the bioavailability of NO and represents a genetic risk factor for increased susceptibility to PE. However, large studies or meta-analysis are necessary to validate these findings.

2001 ◽  
Vol 280 (5) ◽  
pp. R1269-R1275 ◽  
Author(s):  
Michael J. Solhaug ◽  
Usa Kullaprawithaya ◽  
Xui Q. Dong ◽  
Ke-Wen Dong

The postnatal pattern of renal endothelial nitric oxide synthase (eNOS) is unknown. The purpose of this study was to characterize eNOS expression during maturation and compare this to neuronal NOS (nNOS). The experiments measured whole kidney eNOS mRNA expression by RT-PCR and protein content by Western blot, as well as cortical and medullary protein content in piglets at selected postnatal ages and in adult pigs. Whole kidney eNOS mRNA was compared with nNOS. Whole kidney eNOS expression decreased from the newborn to its lowest at 7 days, returning by 14 days to adult levels. This eNOS mRNA pattern contrasted with nNOS, which was highest at birth, and progressively decreased to its lowest level in the adult. At birth, cortical eNOS protein was greater than medullary, contrasting with the adult pattern of equivalent levels. In conclusion eNOS is developmentally regulated during early renal maturation and may critically participate in renal function during this period. The eNOS developmental pattern differs from nNOS, suggesting that these isoforms may have different regulatory factors and functional contributions in the postnatal kidney.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Salah A. Mohamed ◽  
Arlo Radtke ◽  
Roza Saraei ◽  
Joern Bullerdiek ◽  
Hajar Sorani ◽  
...  

Aims. Dysregulated expression of the endothelial nitric oxide synthase (eNOS) is observed in aortic aneurysms associated with bicuspid aortic valve (BAV). We determined eNOS protein levels in various areas in ascending aortic aneurysms.Methods and Results. Aneurysmal specimens were collected from 19 patients, 14 with BAV and 5 with tricuspid aortic valve (TAV). ENOS protein levels were measured in the outer curve (convexity), the opposite side (concavity), the distal and above the sinotubular junction (proximal) aneurysm. Cultured aortic cells were treated with NO synthesis inhibitor L-NAME and the amounts of 35 apoptosis-related proteins were determined. In patients with BAV, eNOS levels were significantly lower in the proximal aorta than in the concavity and distal aorta. ENOS protein levels were also lower in the convexity than in the concavity. While the convexity and distal aorta showed similar eNOS protein levels in BAV and TAV patients, levels were higher in TAV proximal aorta. Inhibition of NO synthesis in aneurysmal aortic cells by L-NAME led to a cytosolic increase in the levels of mitochondrial serine protease HTRA2/Omi.Conclusion. ENOS protein levels were varied at different areas of the aneurysmal aorta. The dysregulation of nitric oxide can lead to an increase in proapoptotic HTRA2/Omi.


2009 ◽  
Vol 2 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Xiongfei Xu ◽  
Zhongzhuang Wang ◽  
Quan Li ◽  
Xiang Xiao ◽  
Qinglin Lian ◽  
...  

Exposure to hyperbaric oxygen (HBO) can lead to seizures. Many studies have demonstrated that there exist a very close relationship between the alteration of cerebral blood flow (CBF) and the onset of seizures. Nitric oxide (NO) may play a key role in the change of CBF during exposure, and modulation of endothelial nitric oxide synthase (eNOS)-derived NO by HBO is responsible for early vasoconstriction, whereas late HBO-induced vasodilation depends upon a large amount of NO from both eNOS and neuronal nitric oxide synthase (nNOS). To investigate the effect of HBO on the activity and expression of eNOS in cerebral microvascular endothelial cells (CMEC) in vitro, primarily cultured CMEC from neonatal rats were exposed to oxygen at 500 kPa [5 atmosphere absolute (ATA)] for 10, 20, 30, 60 and 120 minutes (min), then eNOS activity, protein and mRNA contents in cells were detected. Our results showed that immediately after exposure, 30, 60 and 120 min HBO exposures did not alter NOS activity. When detected no matter immediately or six hours (h) after exposure, these exposures also did not alter eNOS protein and mRNA levels. However, when detected 24 h after exposure, 30, 60 and 120 min exposures upregulated eNOS protein content by 39%, 60% and 40% respectively. 10 and 20 min exposures upregulated eNOS mRNA content by about 15%, while 30, 60 and 120 min exposures upregulated it by about 20–30%. The increased eNOS protein and mRNA contents at 24 h after exposure may reflect new protein synthesis for eNOS. Our studies showed that with the exposing protocols we used, HBO did induce eNOS expression increase in CMEC. However, compared with the decrease of CBF in vivo, which occurred in a relative short time after rat was exposed to HBO above 4 ATA, the responses of eNOS in CMEC in vitro were a little slow. Thus we considered that for the vasodilation in the late period of HBO exposure before seizure, the effect of NO produced by eNOS was limited.


2001 ◽  
Vol 281 (4) ◽  
pp. L1011-L1020 ◽  
Author(s):  
Amy N. MacRitchie ◽  
Kurt H. Albertine ◽  
Jiancheng Sun ◽  
Paul S. Lei ◽  
Suzanne C. Jensen ◽  
...  

Nitric oxide (NO), produced in lung vascular endothelium and airway epithelium, has an important role in regulating smooth muscle cell growth and tone. Chronic lung disease, a frequent complication of premature birth, is characterized by excess abundance, tone, and reactivity of smooth muscle in the pulmonary circulation and conducting airways, leading to increased lung vascular and airway resistance. Whether these structural and functional changes are associated with diminished pulmonary expression of endothelial nitric oxide synthase (eNOS) protein is unknown. Both quantitative immunoblot analysis and semiquantitative immunohistochemistry showed that there was less eNOS protein in the endothelium of small intrapulmonary arteries and epithelium of small airways of preterm lambs that were mechanically ventilated for 3 wk compared with control lambs born at term. No significant differences were detected for other proteins (inducible NOS, α-smooth muscle actin, and pancytokeratin). Lung vascular and respiratory tract resistances were greater in the chronically ventilated preterm lambs compared with control term lambs. These results support the notion that decreased eNOS in the pulmonary circulation and respiratory tract of preterm lambs may contribute to the pathophysiology of chronic lung disease.


Reproduction ◽  
2006 ◽  
Vol 132 (4) ◽  
pp. 579-587 ◽  
Author(s):  
Anna T Grazul-Bilska ◽  
Chainarong Navanukraw ◽  
Mary Lynn Johnson ◽  
Daniel A Arnold ◽  
Lawrence P Reynolds ◽  
...  

This study was conducted to evaluate the expression of endothelial nitric oxide synthase (eNOS) in ovarian follicles and corpora lutea (CL) throughout the estrous cycle in sheep. Three experiments were conducted to (1) immunolocalize eNOS protein, (2) determine expression of mRNA for eNOS and its receptor guanylate cyclase 1 soluble β3 (GUCY1B3), and (3) co-localize eNOS and vascular endothelial growth factor (VEGF) proteins in the follicles and/or CL throughout the estrous cycle. In experiment 1, ovaries were collected from ewes treated with FSH, to induce follicular growth or atresia. In experiment 2, ovaries were collected from ewes treated with FSH and hCG to induce follicular growth and ovulation. In experiment 3, ovaries were collected from superovulated ewes to generate multiple CL on days 2, 4, 10, and 15 of the estrous cycle. In experiments 1 and 2, the expression of eNOS protein was detected in the blood vessels of the theca externa and interna of healthy ovarian follicles. However, in early and advanced atretic follicles, eNOS protein expression was absent or reduced. During the immediate postovulatory period, eNOS protein expression was detected in thecal-derived cells that appeared to be invading the granulosa layer. Expression of eNOS mRNA tended to increase in granulosa cells at 12 and 24 h, and in theca cells 48 h after hCG injection. In experiment 3, eNOS protein was located in the blood vessels of the CL during the estrous cycle. Dual localization of eNOS and VEGF proteins in the CL demonstrated that both were found in the blood vessels.


Sign in / Sign up

Export Citation Format

Share Document