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 2; p =0.004). Finally, a baseline endostatin cut-off point of 184ng/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.