Angiogenesis in symptomatic intracranial atherosclerosis: predominance of the inhibitor endostatin is related to a greater extent and risk of recurrence.
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.
Arenillas
Juan F
JF
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
Alvarez-Sabín
José
J
Montaner
Joan
J
Rosell
Anna
A
Molina
Carlos A
CA
Rovira
Alex
A
Ribó
Marc
M
Sánchez
Esther
E
Quintana
Manuel
M
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*
D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A