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

作者：Navarro Sobrino Miriam; Rosell Anna; Hernandez Guillamon Mar; Penalba Anna; Boada Cristina; Domingues Montanari Sophie; Ribo Marc; Alvarez Sabin Jose; Montaner Joan^*

来源：Atherosclerosis, 2011, 216(1): 205-211.

DOI：10.1016/j.atherosclerosis.2011.01.030

• Angiogenesis
• Stroke
• Outcome
• Endostatin
• Biomarker

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 3 h of symptoms onset), 1, 2, 12, 24 h 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-1 alpha) and inhibitors (endostatin, angiostatin, thrombospondin-1 and thrombospondin-2) were analyzed by Searchlight (R) technology or ELISA. Additionally, baseline and 24 h endostatin plasma level was determined in anewset 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.

• 出版日期2011-5