Association of homocysteine, asymmetric dimethylarginine, and nitric oxide with preeclampsia.
OBJECTIVE
Endothelial dysfunction underlies the pathogenesis of preeclampsia, but its mechanism has not yet been completely understood. In this study we have aimed to measure homocysteine (Hcy), asymmetric dimethylarginine (ADMA), and nitric oxide (NO) levels as endothelial dysfunction markers in preeclamptic women.


METHODS
Control-case study with 62 preeclamptic patients and 30 controls without pregnancy complications was conducted. Plasma total Hcy, determined by capillary column gas chromatography/mass spectrometry (GC/MS), was correlated with serum ADMA (determined by liquid chromatography/tandem mass spectrometry using (13)C(6)-L: -arginine as the internal standard) and NO (analyzed by GC/MS).


RESULTS
There was a highly significant increase in the plasma concentration of homocysteine (P < 0.001) and ADMA (P < 0.001) and a highly significant decrease in the plasma concentration of nitric oxide (P < 0.001) among the preeclamptic patients. The differences were more significant between mild and severe preeclampsia, with and without eclampsia, with and without HELLP (hemolysis, elevated serum level of liver enzymes, and low platelets). In the combined patients and control groups a highly significant positive correlation was found between the plasma concentrations of homocysteine and ADMA (r = 0.853, P < 0.001). In addition, significant negative correlations were detected between the plasma concentrations of nitric oxide and the plasma concentration of homocysteine (r = -0.870, P < 0.001) and ADMA (r = -0.895, P < 0.001). These significant correlations were found to persist, even when they were restricted to the preeclamptic patients.


CONCLUSIONS
The homocysteine-ADMA-NO may be at least partly responsible for etiology in preeclampsia and could be regarded as markers for the severity of the disease. Therefore, L: -arginine may represent a novel therapy for the treatment of preeclampsia.
Mao
Dongwei
D
Department of Obstetrics and Gynecology, The Forth Affiliated Hospital, Harbin Medical University, Harbin, China. lihoqi@yahoo.com.cn
Che
Jianhua
J
Li
Keshen
K
Han
Shiyu
S
Yue
Qi
Q
Zhu
Li
L
Zhang
Wei
W
Li
Lin
L
D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D004730:Endothelium, Vascular / Q000503:physiopathology; D045462:Endothelium-Dependent Relaxing Factors / Q000097:blood; D004791:Enzyme Inhibitors / Q000097:blood*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000097:blood* / Q000378:metabolism; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D045462:Endothelium-Dependent Relaxing Factors; D004791:Enzyme Inhibitors; D006710:Homocysteine; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine