Plasma levels of asymmetric dimethylarginine in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy.
BACKGROUND
Asymmetric dimethylarginine (ADMA) is a marker of endothelial dysfunction and a new independent risk factor for adverse cerebrovascular events in small vessel disease. Conversely, L-arginine (LARG) may have a protective role.


METHODS
To assess ADMA, LARG levels and LARG/ADMA ratio in 16 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and normal controls, and to look for possible correlations with white matter changes. Plasma levels of ADMA and LARG were assayed by high-performance liquid chromatography in all subjects. The overall T(1) and T(2) lesion load was obtained from brain MRI of patients with CADASIL.


RESULTS
ADMA plasma concentrations (1.5 +/- 2.0 microM) were significantly higher (p < 0.05) in CADASIL patients than in controls (0.35 +/- 0.075 microM). Analyzing only CADASIL subjects, an inverse borderline-significant correlation was found between LARG/ADMA (190 +/- 20) and T(2)-weighted lesion volumes (57.9 +/- 46.5; r = -0.578, p = 0.024).


CONCLUSIONS
Our results may indicate the possible coexistence of endothelial dysfunction in CADASIL patients, broadening the range of potentially pathogenetic mechanisms in this disease and providing insights for future therapeutic strategies.
Rufa
Alessandra
A
Dipartimento di Scienze Neurologiche e del Comportamento, Università di Siena, Siena, Italia.
Blardi
Patrizia
P
De Lalla
Arianna
A
Cevenini
Gabriele
G
De Stefano
Nicola
N
Zicari
Enza
E
Auteri
Alberto
A
Federico
Antonio
A
Dotti
Maria Teresa
MT
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D046589:CADASIL / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012307:Risk Factors
D000959:Antihypertensive Agents; D015415:Biomarkers; D008055:Lipids; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; C018524:N,N-dimethylarginine; D001120:Arginine