Endothelial Cell Activation Is Associated with Cerebral White Matter Lesions in Patients with Cerebrovascular Disease

Abstract

Cerebral MRI scanning frequently shows white matter lesions in elderly people. They are related to cognitive impairment and may result in dementia. Although vascular risk factors are associated with the presence of white matter lesions, the exact pathogenesis remains unclear. Animal studies have indicated involvement of endothelial cells in the pathogenesis of white matter lesions and possibly dementia. We investigated the relation between endothelial cell activation and white matter lesions in individuals with cerebrovascular disease. In 29 patients with an acute stroke (n = 11) or TIAs associated with a symptomatic internal carotid artery stenosis (n = 18), markers of endothelial cell activation such as intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, and sP-selectin were measured by means of ELISA. All individuals underwent 1.5-T MRI scanning. White matter lesions were rated for the periventricular and the subcortical region separately. Individuals with severe periventricular white matter lesions had higher levels of sP-selectin (245.5 ng/mL vs. 172.7 ng/mL, p = 0.01) and sVCAM-1 (547.8 ng/mL vs. 454.0 ng/mL, p = 0.04) than those without. This association was only found in individuals with a symptomatic carotid artery stenosis. No such association was found for subcortical white matter lesions. We did not detect any relation between sICAM-1 and sE-selectin and white matter lesions. Endothelial cell activation may play a role in the pathogenesis of white matter lesions, especially in periventricular white matter. Possibly, this activation represents the influence of vascular factors on the cerebral endothelium as a prelude to increasingly severe small vessel disease.

Associations between white matter lesions, cerebrovascular risk factors, and low CSF Aβ42

“…There is a strong correlation between age-related WML and vascular risk factors (de Leeuw et al, 2002). In most patients, cognitive impairment associated with WML is regarded primarily as a vascular cognitive disorder (Roman, 2002;Roman et al, 2004).…”

Living Beyond Our Physiological Means

“…Individuals with severe periventricular white matter lesions and carotid artery stenosis have higher levels of sP-selectin and soluble vascular cell adhesion molecule-1 (sVCAM-1) than those without. 122 Hassan et al have reported that patients with cerebral SVD have elevated plasma levels of markers of endothelial activation and damage such as intracellular adhesion molecule 1, thrombomodulin tissue factor, and tissue factor pathway inhibitor. 123 Van Dijk and colleagues confirmed a relationship between inflammation and the severity and progression of cerebral SVD independent of other cardiovascular risk factors and severity of carotid atherosclerosis.…”

Relation of Brain Natriuretic Peptide Levels to Cognitive Dysfunction in Adults >55 Years of Age With Cardiovascular Disease

“…15 In turn, endothelial abnormalities have recently been linked to cerebrovascular disease and reduced cognitive function. 9,16,17 Further research is needed to clarify the relation between BNP and these possible mechanisms.There are several limitations of the present study. Although BNP levels were significantly related to cognitive performance in the current sample, further examination in larger and more diverse samples would strengthen the generalizability of the findings.…”

“…15 In turn, endothelial abnormalities have recently been linked to cerebrovascular disease and reduced cognitive function. 9,16,17 Further research is needed to clarify the relation between BNP and these possible mechanisms.…”