title: Angiogenesis in symptomatic intracranial atherosclerosis: predominance of the inhibitor endostatin is related to a greater extent and risk of recurrence.
abstract: OBJECTIVE
  Angiogenesis may be beneficial in chronic myocardial and limb ischemia, but its role in intracranial atherosclerosis remains unknown. We aimed to investigate the relationship between the pro-angiogenic vascular endothelial growth factor (VEGF) and the anti-angiogenic endostatin, and the extent and risk of recurrence of symptomatic intracranial atherosclerosis.
  
  
  METHODS
  Of a total of 94 consecutive patients with symptomatic intracranial stenoses, 40 fulfilled all inclusion criteria. Intracranial stenoses were confirmed by magnetic resonance angiography. Magnetic resonance imaging (MRI) including diffusion-weighted sequences was conducted. Plasmatic VEGF and endostatin were determined from blood samples obtained 3 months after stroke onset, and patients were followed-up thereafter.
  
  
  RESULTS
  A total of 144 intracranial stenoses were confirmed (median number per patient=3). Endostatin/VEGF ratio gradually augmented with the increasing number of intracranial stenoses (r=0.35, P=0.02). Diabetes mellitus (OR, 6.04; CI, 1.1 to 32.2; P=0.03) and a higher endostatin/VEGF ratio (OR, 15.7; CI, 2.2 to 112.3; P=0.006) were independently associated with a greater extent of intracranial atherosclerosis. During a median follow-up of 13 months, 8 patients (20%) experienced a new cerebral ischemic event. A higher baseline endostatin concentration was an independent predictor of new events (hazard ratio, 7.24; CI, 1.6 to 33.8; P=0.011) in a Cox regression model after adjustment for age, sex, number of stenotic vessels, and risk factors. Patients with a higher endostatin level had a lower survival free of new events (P=0.01, log-rank test).
  
  
  CONCLUSIONS
  A predominance of the inhibitor endostatin within the endogenous angiogenic response is associated with a greater extent and risk of recurrence of symptomatic intracranial atherosclerosis, suggesting that angiogenesis may be beneficial in this condition.
authors.affiliation: Neurovascular Unit and Neurovascular Research Laboratory, Department of Neurology, Vall d'Hebron Hospital, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. juanfarenillas@terra.es
authors.forename: Juan F
authors.initials: JF
authors.lastname: Arenillas
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.forename: Anna
authors.initials: A
authors.lastname: Rosell
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Alex
authors.initials: A
authors.lastname: Rovira
authors.forename: Marc
authors.initials: M
authors.lastname: Ribó
authors.forename: Esther
authors.initials: E
authors.lastname: Sánchez
authors.forename: Manuel
authors.initials: M
authors.lastname: Quintana
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000453:epidemiology; D018572:Disease-Free Survival; D043169:Endostatins / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D008297:Male; D018919:Neovascularization, Physiologic; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A