Mobilization Of Circulating Endothelial Progenitor Cells In Patients With Acute Ischemic Stroke

BackgroundVascular endothelial dysfunction induce atherosclerosis and thrombosis of vascular occlusion, which plays a key role in acute ischemic stroke (AIS).Endothelial progenitor cells (EPCs), a group of bone marrow-derived CD34+ / KDR+ / CD133+ cells, present in the peripheral circulation with the ability to proliferate and differentiate into endothelial cells. As a cell repository, EPCs can replace endothelial cells which lost function, therefore help to maintain endothelial integrity[1]and prevent the occurrence and development of atherosclerosis. On the other hand, as a response to tissue ischemia, EPCs can be mobilized from bone marrow into peripheral circulation and differentiate into mature endothelial which involved in angiogenesis to promote the recovery of ischemic events[2,3]. Stromal cell-derived factor -1 (SDF-1), one member of CXC chemokine family, can combine with EPCs surface receptor CXCR4 and promote EPCs to homing to ischemic or vascular injury site[4].ObjectivesTo test the hypothesis that EPCs mobilization occurs after acute ischemic stroke, we evaluated the number of EPCs in the process of acute stroke.,meanwhile we determined SDF-1 contnet of in peripherial blood to investigate the mechanism of EPCs Mobilization after AIS.MethodsThis study included consecutively admitted patients with AIS between November 2008 and December 2009 at Second Affiliated Hospital of Chongqing Medical University, Department of Neurology. The level of circulating EPCs (surface markers:CD34/KDR) were examined using flow cytometry at days 1, 7, 14 and 21 after acute stroke. Meanwhile, SDF-1 content was determinated by enzyme-linked immunosorbent assay. EPCs change rate was defined as (EPC14d-EPC1d) and EPC1d ratio. Results(1) Baseline level of circulating EPCs was significantly lower in patients with AIS than the control group (0.022±0.013 vs 0.051±0.020; P<0.01). (2) Based on the Spearman rank correlation analysis,results showed blood pressure, triglyceride, LDL, fasting plasma glucose were negatively correlated (r =-0.953,-0.864, -0.545, -0.623, -0.587; P<0.01)with EPCs counts. Multiple stepwise regression analysis showed systolic blood pressure and LDL as independent predictors of EPCs levels.(3) The mumber of circulating EPCs gradually increased at day 7 after AIS, reached peak level at day 14,and decreased at day 21. EPCs change rate was positively correlated with infarct volume (r = 0.692; P<0.01).(4) The content of SDF-1 significantly increased at day 7 after AIS, reached peak level at day 14,and decreased at day 21. SDF-1 content at day 14 was positively correlated with infarct volume (r = 0.774; P<0.01). (5) EPCs change rate in patients with AIS was positively correlated with SDF-1 content at day 14(r = 0.682; P<0.01).ConclusionsThe Baseline level of circulating EPCs was lower in patients with AIS than control group. SBP and LDL are independent factors of reduced EPCs numbers.An increment of circulating EPCs may result from the mobilization of EPCs in response to stroke stress.The mechanism of EPCs mobilization maybe associated with an increased expression of SDF-1.