Plasma cysteine and glutathione are independent markers of postmethionine load endothelial dysfunction.
OBJECTIVE
Oxidative stress caused by acute hyperhomocysteinemia impairs endothelial function in human arteries. We sought to identify markers of endothelial dysfunction during methionine-induced hyperhomocysteinemia.


METHODS
35 subjects underwent flow-mediated dilation (FMD) of the brachial artery by high-resolution ultrasonography and fasting blood samples before and 3 h postmethionine load (PML). Clinical, conventional biochemical, and redox status (plasma total and reduced homocysteine, glutathione, cysteine, cysteinylglycine, ascorbic acid, alpha-tocopherol, free malondialdehyde, blood glutathione) data were sequentially entered into an univariate and multivariate stepwise linear regression analysis to evaluate their relation with the dependent variable FMD.


RESULTS
Median [interquartile range] FMD decreased from 4.1% [2.8-6.3] to 3.2% [0.7-4.3] PML (P=0.02). At the multivariate analysis PML total cysteine (beta=-0.008, P=0.002) and glutathione (beta=0.21, P=0.005) were the only independent variables associated with FMD after methionine, adjusted for baseline FMD.


CONCLUSIONS
Elevated plasma total cysteine and decreased plasma total glutathione levels were associated with abnormal FMD PML. Cysteine and glutathione are stronger markers of endothelial dysfunction than clinical and all other biochemical variables explored.
Parodi
Oberdan
O
CNR Clinical Physiology Institute-Milan, Department of Cardiology, Niguarda Ca' Granda Hospital, Milan, Italy. ifcnig@tin.it
De Chiara
Benedetta
B
Baldassarre
Damiano
D
Parolini
Marina
M
Caruso
Raffaele
R
Pustina
Linda
L
Parodi
Guido
G
Campolo
Jonica
J
Sedda
Valentina
V
Baudo
Francesco
F
Sirtori
Cesare
C
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000209:etiology; D003545:Cysteine / Q000097:blood*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005978:Glutathione / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008715:Methionine / Q000008:administration & dosage; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011379:Prognosis; D012039:Regional Blood Flow / Q000187:drug effects; D014463:Ultrasonography; D014664:Vasodilation
D015415:Biomarkers; D008715:Methionine; D005978:Glutathione; D003545:Cysteine