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Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis
Ahamad Hassan1, Beverley J Hunt, Michael O'Sullivan
1Department of Clinical Neurosciences, St George's Hospital Medical School, London, UK.
Insights
Cerebral small vessel disease (SVD) involves endothelial dysfunction. Specific markers indicate chronic endothelial damage and prothrombotic changes, particularly in the leukoaraiosis phenotype of SVD.
Area of Science:
- Neurology
- Vascular Biology
- Biomarkers
Background:
- Cerebral small vessel disease (SVD) encompasses lacunar infarction and leukoaraiosis.
- Endothelial dysfunction is implicated in SVD pathogenesis, affecting the blood-brain barrier and cerebral autoregulation.
- Circulating markers of endothelial activation (ICAM1, TM, TF, TFPI) may reveal disease mechanisms.
Purpose of the Study:
- To investigate endothelial dysfunction markers in patients with lacunar stroke.
- To compare marker profiles between isolated lacunar infarction and ischemic leukoaraiosis phenotypes.
- To correlate marker levels with SVD severity.
Main Methods:
- Prospective study of 110 lacunar stroke patients and 50 controls.
- Measurement of intercellular adhesion molecule 1 (ICAM1), thrombomodulin (TM), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) in blood.
- Classification of patients into isolated lacunar infarction or ischemic leukoaraiosis based on MRI findings.
Main Results:
- ICAM1, TM, and TFPI were elevated in SVD patients versus controls.
- The ischemic leukoaraiosis group showed lower TFPI and a higher TF/TFPI ratio compared to the isolated lacunar infarction group.
- TM levels correlated with lacune number and leukoaraiosis severity; TF and TF/TFPI ratio correlated with leukoaraiosis extent.
Conclusions:
- Evidence of chronic endothelial dysfunction exists in cerebral SVD.
- Endothelial prothrombotic changes may drive the ischemic leukoaraiosis phenotype.
- Endothelium-stabilizing therapies could benefit SVD patients, particularly those with leukoaraiosis.
Abstract:
Patients with cerebral small vessel disease (SVD) can present as isolated lacunar infarction or with diffuse white matter changes, with the imaging appearance of leukoaraiosis. Endothelial dysfunction, which can lead to breakdown of the blood-brain barrier, impaired cerebral autoregulation and prothrombotic changes, is believed to be important in mediating disease. Circulating levels of intercellular adhesion molecule 1 (ICAM1), thrombomodulin (TM), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are markers of endothelial activation and damage, and may provide insights into disease pathogenesis or differences between phenotypes. We therefore measured these markers in a prospective series of patients with lacunar stroke. One hundred and ten white Caucasian patients with previous lacunar stroke and 50 community control subjects were studied. Markers of endothelial function were measured on venous blood samples. Patients were classified on brain imaging into two groups: isolated lacunar infarction (n = 47) and ischaemic leukoaraiosis, defined as a clinical lacunar stroke and leukoaraiosis on brain imaging (n = 63). The number of lacunes and severity of leukoaraiosis were also scored on MRI. ICAM1, TM and TFPI were elevated in cerebral SVD subjects compared with controls (P