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Angiogenesis in symptomatic intracranial atherosclerosis: predominance of the inhibitor endostatin is related to a greater extent and risk of recurrence.

AbstractBACKGROUND AND PURPOSE:
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.
AuthorsJuan F Arenillas, José Alvarez-Sabín, Joan Montaner, Anna Rosell, Carlos A Molina, Alex Rovira, Marc Ribó, Esther Sánchez, Manuel Quintana
JournalStroke (Stroke) Vol. 36 Issue 1 Pg. 92-7 (Jan 2005) ISSN: 1524-4628 [Electronic] United States
PMID15550686 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Endostatins
  • Vascular Endothelial Growth Factor A
Topics
  • Aged
  • Brain Ischemia (epidemiology)
  • Disease-Free Survival
  • Endostatins (blood)
  • Female
  • Follow-Up Studies
  • Humans
  • Intracranial Arteriosclerosis (diagnosis)
  • Magnetic Resonance Imaging
  • Male
  • Neovascularization, Physiologic
  • Prospective Studies
  • Recurrence
  • Risk Factors
  • Vascular Endothelial Growth Factor A (blood)

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