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(Stroke. 2005;36:92.)
© 2005 American Heart Association, Inc.

Original Contributions

Angiogenesis in Symptomatic Intracranial Atherosclerosis

Predominance of the Inhibitor Endostatin Is Related to a Greater Extent and Risk of Recurrence

Juan F. Arenillas, MD, PhD; José Álvarez-Sabín, MD, PhD; Joan Montaner, MD, PhD; Anna Rosell; Carlos A. Molina, MD, PhD; Alex Rovira, MD; Marc Ribó, MD; Esther Sánchez, MD Manuel Quintana

From the Neurovascular Unit and Neurovascular Research Laboratory (J.F.A., J.A.-S., J.M., A.R., C.A.M., M.R., M.Q.), Magnetic Resonance Unit (A.R., E.S.), Vall d’Hebron Universitary Hospital, Barcelona, Spain.

Correspondence to Dr Juan F. Arenillas Lara, Neurovascular Unit, Department of Neurology, Vall d’Hebron Hospital, Universitat Autònoma de Barcelona, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain. E-mail juanfarenillas{at}terra.es

Background 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.

Key Words: angiogenesis • atherosclerosis, intracranial • endostatins • intracranial stenosis • vascular endothelial growth factor

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