title: Circulating CD133+CD34+ progenitor cells inversely correlate with soluble ICAM-1 in early ischemic stroke patients.
abstract: OBJECTIVE
  Both endothelial progenitor cells (EPC) and markers of neuroinflammation are candidate biomarkers for stroke severity and outcome prediction. A relationship between EPC and neuroinflammatory markers in early stroke is not fully elucidated. The objectives were to investigate correlations between EPC and neuroinflammation markers (adhesion molecules ICAM-1, VCAM-1, E-selectin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, endothelin (ET)-1, markers of tissue injury (matrix metalloproteinases (MMP)-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1) in early stroke patients.
  
  
  METHODS
  We prospectively recruited symptomatic patients with ischemic cerebrovascular disease. We assessed stroke severity by using of acute (diffusion-weighted imaging (DWI) and final lesion volumes (fluid attenuated inversion recovery (FLAIR). We measured serum soluble ICAM-1, VCAM-1, E-selectin, MMP-9, TIMP-1 and plasma TNF-α, IL-6, ET-1 by ELISA, and quantified EPC in mononuclear fraction of peripheral blood on days 1 and 3 in 17 patients (mean(SD) age 62(14), with admission National Institutes of Health Stroke Scale (NIHSS) 10(8)) selected from 175 patients with imaging confirmed ischemic stroke. Non-parametric statistics, univariate and multivariate analysis were used.
  
  
  RESULTS
  Only ICAM-1 inversely correlated with EPC subset CD133+CD34+ on day 1 (Spearman r = -0.6, p < 0.01) and on day 3 (r = -0.967, p < 0.001). This correlation remained significant after adjustment for age and NIHSS (beta -0.992, p < 0.004), for glucose and systolic blood pressure (beta -0.86, p < 0.005), and for white blood cells and hematocrit (beta -1.057, p < 0.0001) on day 3. MMP-9 (r = 0.509, p < 0.04) and MMP-9/TIMP-1 (r = 0.59, p < 0.013) on day 1 correlated with acute lesion volume. Both IL-6 (r = 0.624, p < 0.01) and MMP-9/TIMP-1 (r = 0.56, p < 0.02) correlated with admission NIHSS.
  
  
  CONCLUSIONS
  Our study showed that high ICAM-1 is associated with low CD133+CD34+subset of EPC. Biomarkers of neuroinflammation may predict tissue injury and stroke severity in early ischemia.
authors.affiliation: Stroke Diagnostics and Therapeutics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1401, USA. Tanya.Bogoslovsky.CTR@usuhs.mil
authors.forename: Tanya
authors.initials: T
authors.lastname: Bogoslovsky
authors.forename: Maria
authors.initials: M
authors.lastname: Spatz
authors.forename: Aneeka
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.forename: Marie
authors.initials: M
authors.lastname: Luby
authors.forename: Joseph
authors.initials: J
authors.lastname: Frank
authors.forename: Steven
authors.initials: S
authors.lastname: Warach
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications / Q000473:pathology; D002465:Cell Movement; D003710:Demography; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D012307:Risk Factors; D012995:Solubility; D013234:Stem Cells / Q000378:metabolism*; D020521:Stroke / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D019715:Tissue Inhibitor of Metalloproteinase-1; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9