Changes in serum vascular endothelial growth factor and endostatin concentrations associated with circulating endothelial progenitor cells after acute ischemic stroke.

Abstract

Angiogenesis is an important pathophysiological response to cerebral ischemia, and can be modulated by vascular endothelial growth factor (VEGF) and endostatin. Circulating endothelial progenitor cells (EPCs) also play an important role as an endogenous repair mechanism for ischemic injury. We sought to investigate early changes in the expression of VEGF and endostatin in serum and the circulating EPCs in patients with acute ischemic stroke (AIS) and analyzed the relations between them. The peripheral blood and serum samples were obtained from 30 patients at 1, 3, 5 and 7 d after AIS. Flow cytometry was used to quantify EPCs, and VEGF and endostatin were measured by enzyme linked immunosorbent assay. Correlation analysis was performed to assess the relations between them. Receiver operating characteristic (ROC) curve was used to appraise the value of EPCs levels in predicting the 90-day prognosis after AIS. Compared with control subjects, circulating EPCs numbers increased from a very lower initial level (P < 0.001) until 7 d after AIS. Serum VEGF and endostatin levels increased and peaked at 3 d and 5 d post-stroke (both P < 0.001), respectively. A significant correlation (P = 0.001) was found between peak serum VEGF concentration and peak endostatin concentration. VEGF/endostatin ratio at day 1 and day 3 after AIS significantly correlated with circulating EPCs numbers at day 5 (P < 0.001) and day 7 post-stroke (P < 0.001). ROC curve analysis suggested that circulating EPCs number at day 7 had a significantly predictive power for good prognosis. VEGF and endostatin may mediate EPCs proliferation in the early phase of ischemic stroke, and the circulating EPCs levels can be a predictor of clinical outcome in AIS.