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Is the Asymmetric Dimethylarginine (ADMA) the Possible Molecule Driving Endothelial Damage in Young Asymptomatic Patients with Cerebral Small Vessel Disease?
Author(s) -
Cifu’ Adriana,
Fabris Martina,
Janes Francesco,
Pessa Maria Elena,
Domenis Rossana,
Nilo Anna Carmen,
Giacomello Roberta,
Gigli Gian Luigi,
Curcio Francesco
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.496.49
Subject(s) - medicine , von willebrand factor , endothelial dysfunction , asymmetric dimethylarginine , fibrinogen , population , lupus anticoagulant , plasminogen activator , inflammation , endothelial activation , immunology , pathology , gastroenterology , platelet , chemistry , thrombosis , biochemistry , environmental health , amino acid , arginine
Cerebral small vessel disease (CSVD), detected as white matter hyperintensities (WMH) on brain MRI, could be a distinct pathological entity within cerebrovascular diseases. CSVD has a high prevalence in aging population and in stroke patients. In the last years, the increasing use of MRI has led to more incidental finding also in young people without classical vascular risk factor. Our intent was to investigate different pathways implicated in endothelial dysfunction such as inflammation, autoimmunity, coagulation, nitric oxide pathway, in a well selected, homogeneous population of patients with WMH, without significant vascular risk factors or neurological diseases. We selected 35 consecutive patients with evidence of CSVD features at brain MRI and 35 controls age‐sex matched. We evaluated markers for thrombophilia (antithrombin III, protein C, protein S, fibrinogen, plasminogen activator inhibitor – 1, tissue plasminogen activator, von Willebrand factor, homocysteine, C‐reactive protein) and autoimmunity (ANA, ENA, anti‐phospholipids antibodies, lupus anticoagulant) using diagnostic assays. In addition, we evaluated several markers of endothelial activation and inflammation. Interleukin 6, interleukin 10, E‐selectin, P‐selectin and asymmetrical dimethylarginine (ADMA) were assayed by ELISA. Platelet Activating Factor‐Acetyl Hydrolase and nitric oxide were measured with a colorimetric assay, while vascular cell adhesion molecule‐1 and intercellular adhesion molecule‐1 were assayed by Luminex® assay. Statistical analyses were conducted with SPSS 20 (SPSS Inc., Chicago USA). We did not find any significant difference between patients and controls, except for ADMA. Indeed, patients displayed significantly higher levels of ADMA (71.97 ± 36.49 vs 44.46 ± 29.94, p=0.002) than controls. ADMA levels showed positive correlation with the total Fazekas score (r = 0,304; p = 0,01). ROC curve analysis showed a moderate accuracy in discriminating patients and controls (AUC = 0,70; CI 0,57–0,82; p = 0,004): a cut‐off of 46 ng/ml is associated with 80% sensitivity but limited (54%) specificity. In this very large biomarker study, ADMA results the only endothelial marker significantly associated to WMH. This reinforces the hypothesis of the key role of endothelial dysfunction and nitric oxide pathway in CSVD. Further studies should explore the cause‐effect relationship between ADMA pathway and CSVD in selected groups of subjects. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .