title: A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke.
abstract: BACKGROUND
  The induction of angiogenesis after stroke may enhance neurorestorative processes. Our aim was to examine the endogenous angiogenesis balance and their association with long-term clinical outcome in ischemic stroke patients.
  
  
  METHODS
  A total of 109 stroke subjects were included in the study. Firstly, plasma samples were obtained from control subjects (n = 26) and tPA-treated stroke patients (n = 29) at baseline (within 3h of symptoms onset), 1, 2, 12, 24h after tPA treatment, at discharge and 3 months after the ischemic event. Angiogenic promoters (PDGF-AA, PDGF-BB, HGF, FGF, KGF, HB-EGF, TPO, VEGF, VEGFR-1, VEGFR-2 and SDF-1α) and inhibitors (endostatin, angiostatin, thrombospondin-1 and thrombospondin-2) were analyzed by Searchlight(®) technology or ELISA. Additionally, baseline and 24h endostatin plasma level was determined in a new set of stroke patients (n = 80). Clinical parameters (NIHSS, mRS, mortality and hemorrhagic transformation events) were assessed to evaluate outcome.
  
  
  RESULTS
  Baseline PDGF-BB, endostatin and thrombospondin-2 levels were higher in stroke patients than in controls (p < 0.05). A pro-angiogenic balance was associated with lower NIHSS scores and less intracranial hemorrhagic complications. Interestingly, a high baseline endostatin level was associated to long-term functional dependency (mRS > 2; p = 0.004). Finally, a baseline endostatin cut-off point of 184 ng/mL was an independent predictor of functional dependency at three months in the multiple logistic regression with an odds ratio of 8.9 (95% CI: 2.7-28.8; p = 0.0002).
  
  
  CONCLUSIONS
  Our results indicate that an early pro-angiogenic balance is associated with mild short-term neurological deficit, while an acute anti-angiogenesis status determined by high endostatin plasma level predicts a worse long-term functional outcome.
authors.affiliation: Neurovascular Research Laboratory and Neurovascular Unit, Neurology and Medicine Department-Universitat Autònoma de Barcelona, Research Institute of the Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Míriam
authors.initials: M
authors.lastname: Navarro-Sobrino
authors.forename: Anna
authors.initials: A
authors.lastname: Rosell
authors.forename: Mar
authors.initials: M
authors.lastname: Hernández-Guillamon
authors.forename: Anna
authors.initials: A
authors.lastname: Penalba
authors.forename: Cristina
authors.initials: C
authors.lastname: Boada
authors.forename: Sophie
authors.initials: S
authors.lastname: Domingues-Montanari
authors.forename: Marc
authors.initials: M
authors.lastname: Ribó
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D042501:Angiogenic Proteins / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D004185:Disability Evaluation; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D016017:Odds Ratio; D011237:Predictive Value of Tests; D020127:Recovery of Function; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator