Molecular markers of endothelial dysfunction in acute ischemic stroke

INTRODUCTION: In spite of all similarities, ischemic stroke cases representing 80% of the acute cerebrovascular accidents, different steps of platelet activation, coagulation and fibrinolytic cascade are involved in the pathomechanism of the different stroke subtypes. The differentiation of the atherothrombotic, cardioembolic and lacunar forms of acute ischemic stroke is based on the comprehensive evaluation of clinical signs, neuroimaging technics, and diagnostic ultrasound, but also a significant effort was made to characterize the specificities of the underlying processes of the coagulation system by signal molecules, in order to clarify their possible role and to support the diagnostic and therapeutic decisions. PATIENTS AND METHODS: The von Willebrand factor was studied as the marker of endothelial injury in 34 acute ischemic stroke patients within 24 hours after the onset of their stroke, and repeatedly 2, 4, and 12 weeks thereafter. To determine the probable source of the von Willebrand factor, usually released not only by endothelial cells, but also by platelets, the authors simultaneously measured the levels of an additional endothelial marker, thrombomodulin, and a platelet activation marker, beta-thromboglobulin. RESULTS: The mean of von Willebrand factor levels measured in stroke patients on the first day was 123%, whereas the mean of the control group 72% (p < 0.05). There was no significant difference according to stroke subtype. Von Willebrand values determined two weeks later showed a further 60% increase in stroke patients, and after a gradual fall their level remained above the concentration of the control group. The beta-thromboglobulin level measured in stroke group was significantly higher, than in control individuals (171 IU/ml vs. 32 IU/ml, p < 0.001). This was characteristic for atherothrombotic and cardioembolic stroke, but not for lacunar infarctions. If measured repeatedly, beta-thromboglobulin levels decreased rapidly in the first two weeks, than somewhat slower. Soluble thrombomodulin was slightly elevated in stroke patients (4.24 ng/ml) compared to healthy subjects (3.81 ng/ml), without statistical significance, and without major differences between subgroups. CONCLUSIONS: While early determination of beta-thromboglobulin can contribute to the differential diagnoses of the subtypes of ischemic stroke, the long-lasting elevation of von Willebrand factor may reflect endothelial dysfunction caused by several factors in the microvasculature of the penumbra.