title: Temporal profile of molecular signatures associated with circulating endothelial progenitor cells in human ischemic stroke.
abstract: Endothelial progenitor cells (EPC) have been associated with good functional outcome in ischemic stroke. From preclinical studies, it has been reported that EPC proliferation is mediated by several molecular markers, including vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1α), and the activity of matrix metalloproteinase-9 (MMP-9). Therefore, our aim was to study the role of these molecular factors in EPC proliferation in human ischemic stroke. Forty-eight patients with first episode of nonlacunar ischemic stroke were prospectively included in the study within 12 hr of symptom onset. EPC colonies were classified as early-outgrowth colony forming unit-endothelial cell (CFU-EC) and quantified at admission, at 24 and 72 hr, at day 7, and at 3 months. At the same time, serum levels of VEGF, SDF-1α, and active MMP-9 were measured by ELISA. The primary endpoint was EPC increment during the first week, which was defined as the difference in the number of CFU-EC between day 7 and admission. We found that VEGF (r = 0.782), SDF-1α (r = 0.828), and active MMP-9 (r = 0.740) levels at 24 hr from stroke onset showed a strong correlation with EPC increment. Similar results were found for VEGF levels at 72 hr (r = 0.839) and at day 7 (r = 0.602) as well as for active MMP-9 levels at 72 hr (r = 0.442) and at day 7 (r = 0.474). In the multivariate analyses, serum levels of VEGF at 72 hr (B: 0.074, P < 0.0001) and SDF-1α at 24 hr (B: 0.049, P = 0.008) were independent factors for EPC increment during the first week of evolution. These findings suggest that VEGF and SDF-1α may mediate EPC proliferation in human ischemic stroke.
authors.affiliation: Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Sobrino
authors.forename: María
authors.initials: M
authors.lastname: Pérez-Mato
authors.forename: David
authors.initials: D
authors.lastname: Brea
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Yáñez
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanco
authors.forename: José
authors.initials: J
authors.lastname: Castillo
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000097:blood* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000097:blood; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020127:Recovery of Function; D013234:Stem Cells / Q000378:metabolism*; D020521:Stroke / Q000097:blood* / Q000473:pathology; D059467:Transcriptome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D054377:Chemokine CXCL12; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9