Biomarkers of Endothelial Dysfunction in Cerebral Small Vessel Disease

Endothelial dysfunction (ED) plays a significant role in the development of cerebral small vessel disease (SVD). Analyzing biomarkers related to endothelial function, obtainable from peripheral blood, offers valuable insights for researchers. However, the link between biomarkers of ED and cerebral SVD remains controversial.Our primary aim was to investigate the relationship between the biomarkers of ED by 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.

Patients with cerebral SVD were grouped according to their symptoms. We compared the serum biomarkers of ED between patient groups. All biomarkers except CRP were studied using enzyme-linked immunosorbent assay. We also performed a correlation analysis between cerebral SVD biomarkers in neuroimaging and ED biomarkers.

We included 68 patients in this study. 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 (EPVSs) in the basal ganglia score positively but slightly correlated with serum ADMA levels.

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.