Level and Value of Circulating Endothelial Progenitor Cells in Patients After Acute Ischemic Stroke

Abstract

Endothelial progenitor cells (EPCs) migrate from bone marrow to systemic circulation in response to tissue ischemia where they differentiate into mature endothelial cells for angiogenesis in situ. This study tested the hypothesis that the level of circulating EPCs is substantially increased and predictive of prognostic outcomes after acute ischemic stroke (IS). The level of circulating EPCs (staining markers: CD31/CD34 [E(1)], CD62E/CD34 [E(2)], and KDR/CD34 [E(3)]) were examined using flow cytometry at 48 hours after acute IS in 138 consecutive patients. The EPC level was also evaluated once in 20 healthy volunteers and in 40 at-risk control subjects. Level of circulating EPCs (E(1-3)) was significantly higher in patients with IS than in at-risk control subjects (P<0.05). Additionally, EPC (E(1-3)) level was significantly lower in patients with severe neurological impairment (defined as a score >or=12 on the National Institutes of Health Stroke Scale) than in patients with less severe impairment (National Institutes of Health Stroke Scale < score 12) at 48 hours after IS (P<0.0001). Moreover, the EPC (E(3)) level was strongly correlated with improved National Institutes of Health Stroke Scale >or=4 on day 21 after IS (P=0.0004). Furthermore, low circulating EPC level was independently predictive of severe neurological impairment (National Institutes of Health Stroke Scale >or=12) at 48 hours (E(1-3)) and combined major adverse clinical outcomes (defined as recurrent IS, any cause of death, or National Institutes of Health Stroke Scale of >or=12) on day 90 (E(1)) after IS (P<0.001). Level of circulating EPCs is independently predictive of prognosis after IS.