The role of homocysteine, asymmetric dimethylarginine and nitric oxide in pre-eclampsia

Demir, Bilge Çetinkaya; Demir, Sedat; Paşa, Semir; Güven, Süleyman; Atamer, Yıldız; Atamer, Aytaç; Koçyiğit, Yüksel

doi:10.3109/01443615.2012.693985

Cited by 23 publications

(19 citation statements)

References 41 publications

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“…In concordance with previous studies (Burgoon and others, 2002), we found that there was a significant increase in plasma homocysteine in pregnant mice administered a FD+SS diet throughout both the preconceptional and gestational period. The relationship between high homocysteine and poor pregnancy outcomes, independent of blood folate, has been established in both animal models and in human clinical populations (Bergen and others, 2012; Demir and others, 2012; Dhobale and others, 2012; Gadhok and others, 2011; Kim and others, 2012; van Mil and others, 2010). Administration of homocysteine to pregnant mice in the early stages of gestation has been demonstrated to cause fetal growth restriction, congenital abnormalities and increased fetal lethality (Han and others, 2009).…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies against homocysteinylated protein in a mouse model of folate deficiency‐induced neural tube defects

Denny

Kelly

Kumar

et al. 2016

Birth Defects Research

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Periconceptional supplementation with folic acid results in a significant reduction in the incidence of neural tube defects (NTDs). Nonetheless, NTDs remain a leading cause of perinatal morbidity and mortality worldwide, and the mechanism(s) by which folate exerts its protective effects are unknown. Homocysteine is an amino acid that accumulates under conditions of folate-deficiency, and is suggested as a risk factor for NTDs. One proposed mechanism of homocysteine toxicity is its accumulation into proteins in a process termed homocysteinylation. Herein, we used a folate-deficient diet in pregnant mice to demonstrate that there is: (i) a significant inverse correlation between maternal serum folate levels and serum homocysteine; (ii) a significant positive correlation between serum homocysteine levels and titers of autoantibodies against homocysteinylated protein; and (iii) a significant increase in congenital malformations and NTDs in mice deficient in serum folate. Further, in mice administered the folate-deplete diet prior to conception, supplementation with folic acid during the gestational period completely rescued the embryos from congenital defects, and resulted in homocysteinylated protein titers at term that are comparable to that of mice administered a folate-replete diet throughout both the pre- and post-conception period. These results demonstrate that a low-folate diet that induces NTDs also increases protein homocysteinylation and the subsequent generation of autoantibodies against homocysteinylated proteins. These data support the hypotheses that homocysteinylation results in neo-self antigen formation under conditions of maternal folate deficiency, and that this process is reversible with folic acid supplementation.

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Section: Discussionmentioning

confidence: 99%

Autoantibodies against homocysteinylated protein in a mouse model of folate deficiency‐induced neural tube defects

Denny

Kelly

Kumar

et al. 2016

Birth Defects Research

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“…It has also been suggested that disturbances in the homocysteine-ADMA-NO pathway may be at least partly responsible for the etiology of preeclampsia and could be regarded as markers for the severity of the disease [24]. Homocysteine inhibits the expression and activity of dimethylamino dimethyl hydrolase (DDAH), the enzyme hydrolyzing and degrading ADMA to citrulline and dimethylamine [10,21,25,26]. Because of this metabolic relation, it has been suggested that ADMA is a mediator of endothelial dysfunction in hyperhomocysteinemia [25].…”

Section: Discussionmentioning

confidence: 99%

“…Nitric oxide (NO) regulates the placental blood flow and actively participates in trophoblast invasion and placental development [9]. One theory (of many) suggests that clinical manifestations of preeclampsia caused by failure of the placental vasculature and endothelial malfunction, including insufficient nitric oxide synthesis or NO bioavailability, may contribute to increased blood pressure, systemic vascular resistance, and sensitivity to the pressors [4,10–13]. …”

Section: Introductionmentioning

confidence: 99%

“…Nitric oxide is the key transmitter for the endothelium-dependent regulation of the vascular tone and it regulates blood pressure, abolishes the toxic activity of superoxide ions, inhibits the adhesion and activation of platelet aggregation, and acts as an anticoagulant and antiatherogenic substance [10,14]. Nitric oxide contributes to the vasodilatation of blood vessels and to the decrease in vascular resistance observed during normal pregnancy [10,13,15]. Nitric oxide is produced in intact endothelial cells by endothelial NO synthase (eNOS) as the key enzyme from L-arginine [14,15].…”

Section: Introductionmentioning

confidence: 99%

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A comparison of maternal serum levels of endothelial nitric oxide synthase, asymmetric dimethylarginine, and homocysteine in normal and preeclamptic pregnancies

Laskowska

Laskowska²,

Terbosh³

et al. 2013

Med Sci Monit

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BackgroundThe aim of this study was to determine the maternal serum concentrations of eNOS, ADMA, and homocysteine in preeclamptic pregnancies.Material/MethodsThe study was carried out on 62 patients with pregnancy complicated by early onset and 53 patients with late onset preeclampsia. The control group consisted of 65 healthy normotensive pregnant patients. The serum eNOS, ADMA and homocysteine concentrations were determined using ELISA assays.ResultsOur study revealed elevated levels of homocysteine and ADMA in the serum of women with preeclampsia. The highest levels were observed in patients with early onset preeclampsia, but the differences between both groups of preeclamptic patients with early and late onset of preeclampsia were not statistically significant. Both groups of preeclamptic women had slightly lower levels of maternal serum endothelial nitric oxide synthase than in normotensive pregnant women, but these differences were not statistically significant.ConclusionsThe higher levels of homocysteine and ADMA observed in patients with early onset preeclampsia may suggest that higher levels of maternal serum homocysteine and ADMA correlate with the severity, and may determine the earlier clinical onset of the disease. The elevated levels of ADMA and the unchanged levels of eNOS in preeclamptic pregnancies suggest that NO deficiency in this pregnancy disorder results not from a reduced level or activity of eNOS, but from elevated levels of ADMA, an endogenous eNOS inhibitor. The lowering of increased levels of homocysteine and ADMA may be helpful in therapy of vascular disturbances occurring in preeclampsia.

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“…Moreover, the level of VEGF was significantly lower in the artery but not in the vein in preeclampsia cases [22]. Other studies indicated an increase in ADMA level and a decrease in NO levels [23] or decrease in the level of both factors [24] in preeclampsia. Furthermore, the importance of NO has been emphasized in preeclampsia [25, 26].…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of Asymmetric Dimethylarginine, Vascular Endothelial Growth Factor, and Nitric Oxide Metabolite Levels in Preeclampsia Patients

Noorbakhsh

Kianpour

Nematbakhsh

2013

ISRN Obstetrics and Gynecology

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Background. Hypertensive disorder generally complicates 5–10 percent of all pregnancies. Angiogenic growth factors may be helpful for the diagnosis and prediction of preeclampsia. Therefore, in this study we attempted to determine the serum levels of asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), and nitric oxide (NO) metabolite (nitrite) in preeclampsia patients and compared the levels with those obtained from normal pregnant women. Methods. Ninety pregnant women (19–33 years old) in two groups of preeclampsia and normal were considered during 2012. The levels of ADMA, VEGF, and nitrite were measured in maternal serum samples using ELISA kits. Results. Significant increase of VEGF and nitrite levels was observed in preeclampsia patients when compared with other groups (P < 0.05). The serum level of ADMA demonstrated a similar increased trend in preeclampsia patients; however, the increase was not statistically significant (P = 0.08). Conclusion. The findings reveal that the elevation of serum levels of VEGF and nitrite and possibly ADMA may be involved in the pathogenesis of preeclampsia.

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The role of homocysteine, asymmetric dimethylarginine and nitric oxide in pre-eclampsia

Cited by 23 publications

References 41 publications

Autoantibodies against homocysteinylated protein in a mouse model of folate deficiency‐induced neural tube defects

Autoantibodies against homocysteinylated protein in a mouse model of folate deficiency‐induced neural tube defects

A comparison of maternal serum levels of endothelial nitric oxide synthase, asymmetric dimethylarginine, and homocysteine in normal and preeclamptic pregnancies

Serum Levels of Asymmetric Dimethylarginine, Vascular Endothelial Growth Factor, and Nitric Oxide Metabolite Levels in Preeclampsia Patients

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