Circulating Endothelial Microparticles as a Marker of Cerebrovascular Disease

Objective: Circulating endothelial microparticles (EMPs) have been reported to reflect vascular damage. Detailed profiling of these blood endothelial markers may adumbrate the pathogenesis of stroke or enable determination of the risk for stroke. We investigated EMP profiles in patients at risk for cerebrovascular disease. Methods: We prospectively examined 348 consecutive patients: 73 patients with acute stroke and 275 patients with vascular risk factors but no stroke events. We quantified various types of EMPs by flow cytometry using CD31, CD42b, annexin V (AV), and CD62E antibodies in the peripheral blood of patients. This method allowed fractionation of CD31(+)/CD42b(-), CD31(+)/AV(+), and CD62E(+) EMPs. Clinical and laboratory factors associated with EMPs were assessed. Results: Recent ischemic episodes were found to be more strongly associated with greater CD62E(+) EMP levels than with levels of other phenotypes. Increased National Institutes of Health Stroke Scale scores and infarct volumes in acute stroke patients were significantly associated with greater CD62E(+) EMP levels. In the risk factor group, patients with extracranial arterial stenosis had greater CD62E(+) EMP levels, whereas those with intracranial arterial stenosis had greater CD31(+)/CD42b(-) and CD31(+)/AV(+) EMP levels. The ratio of CD62E(+) to CD31(+)/CD42b(-) or CD31(+)/AV(+) EMP level significantly discriminated extracranial and intracranial arterial stenosis. Interpretation: Circulating EMP phenotypic profiles reflect distinct phenotypes of cerebrovascular disease and are markers of vascular pathology and an increased risk for ischemic stroke.