Plasma asymmetric dimethylarginine (ADMA), nitrate and the indices of low-density lipoprotein oxidation.
BACKGROUND
Oxidative modification of low-density lipoprotein (LDL) is an important contributor to atherosclerosis. Also, oxidized LDL is suspected to cause accumulation of asymmetric dimethylarginine (ADMA), an endogenous competitive nitric oxide synthase inhibitor, which is suggested to be an independent risk factor for atherosclerosis. This study was performed to evaluate how plasma ADMA is related to plasma nitric oxide production, oxidized LDL and ex vivo susceptibility of LDL to oxidation in mildly hypercholesterolemic otherwise healthy subjects.


METHODS
Plasma ADMA was determined using high performance liquid chromatography tandem mass spectrometry. LDL oxidation was estimated by the lag time and rate of copper-induced LDL oxidation. The nitric oxide production in plasma was estimated based on nitrate (NO(3)(-)) determination and plasma oxidized LDL was determined by a capture ELISA.


RESULTS
Low ADMA was a significant determinant for high LDL oxidation rate and concentration of plasma ADMA was associated with nitrate levels.


CONCLUSIONS
There may be an interplay between LDL fatty acid oxidation rate and plasma ADMA and nitrate. We hypothesize that plasma ADMA has a bivalent role: high ADMA may have a protective role in decelerating LDL fatty acid oxidation and also a risk factor for endothelial dysfunction by decreasing availability of nitric oxide.
Päivä
Hannu
H
Department of Internal Medicine, University Hospital of Tampere, Tampere, Finland. hannu.paiva@uta.fi <hannu.paiva@uta.fi>
Laakso
Juha
J
Ruokonen
Inkeri
I
Luomala
Mari
M
Saarela
Marika
M
Solakivi
Tiina
T
Metso
Saara
S
Nikkilä
Matti
M
Wuolijoki
Erkki
E
Laaksonen
Reijo
R
Lehtimäki
Terho
T
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D015227:Lipid Peroxidation / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009566:Nitrates / Q000097:blood*; D009569:Nitric Oxide / Q000097:blood; D012307:Risk Factors
D008077:Lipoproteins, LDL; D009566:Nitrates; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine