A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke

Atherosclerosis. 2011 May;216(1):205-11. doi: 10.1016/j.atherosclerosis.2011.01.030. Epub 2011 Jan 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenic Proteins / blood*
  • Biomarkers / blood
  • Brain Ischemia / blood
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / mortality
  • Brain Ischemia / physiopathology
  • Disability Evaluation
  • Drug Administration Schedule
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Neovascularization, Physiologic*
  • Odds Ratio
  • Predictive Value of Tests
  • Recovery of Function
  • Risk Assessment
  • Risk Factors
  • Spain
  • Stroke / blood
  • Stroke / drug therapy*
  • Stroke / mortality
  • Stroke / physiopathology
  • Thrombolytic Therapy*
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Treatment Outcome


  • Angiogenic Proteins
  • Biomarkers
  • Fibrinolytic Agents
  • Tissue Plasminogen Activator