Biomarkers of endothelial dysfunction in cerebral small vessel disease

Abstract

Objective: Our primary aim was to investigate the relationship between the biomarkers of endothelial dysfunction (ED) using analyzing intercellular adhesion molecule-1 (ICAM-1), plasminogen activator inhibitor-1 (PAI-1), asymmetric dimethylarginine (ADMA), interleukin-6 (IL-6), C-reactive protein (CRP) and specific clinical findings of cerebral small vessel disease (SVD), such as the presence of minor stroke or cognitive impairment. We also performed a correlation analysis between ED biomarkers and neuroimaging markers of cerebral SVD. Material and Methods: Patients with cerebral SVD were grouped according to their symptoms. We compared the serum biomarkers of ED between patient groups. We also performed a correlation analysis between cerebral SVD biomarkers in neuroimaging and ED biomarkers. Results: We included 68 patients in this study. Median values of PAI-1, ICAM-1, and ADMA in the whole patient group were abnormally high compared to the reference values of the laboratory. Patients with minor stroke or cognitive deficits had lower levels of PAI-1 than asymptomatic patients, and this finding was more evident in patients with cognitive deficits. Enlarged perivascular spaces in the basal ganglia score positively but slightly correlated with serum ADMA levels. Conclusions: PAI-1 has a possible neuroprotective effect against the development of cognitive impairment in cerebral SVD. Biomarkers of ED differ according to the severity, and localization of the lesions. There was a specific relationship between ADMA and EPVSs in basal ganglia, -not EPVSs in the centrum semiovale- irrespective of vascular risk factors suggesting EPVSs in the centrum semiovale and basal ganglia may be the product of different pathological processes.