Matrix metalloproteinase-3 and intracranial arterial dolichoectasia.
OBJECTIVE
Intracranial arterial dolichoectasia (IADE), also called dilatative arteriopathy of the brain, is defined as an increase in length and diameter of intracranial arteries. Abdominal aortic aneurysm and ectasia of coronary arteries have been reported in association with IADE. In both conditions, a dysfunction of matrix metalloproteinases (MMP)-2, -3, and -9 have been found. Our aim was to investigate these MMP pathways in stroke patients with IADE.


METHODS
Five hundred ten Caucasians patients with brain infarction were consecutively recruited at 12 centers. The diagnosis of IADE was made by consensus between 2 neurologists based on magnetic resonance imaging scans. Determination of MMP-2, -3, and -9 plasma levels was centralized in 1 laboratory. Because we found a threshold effect of MMP-3 plasma levels with the risk of IADE, determination of the MMP-3 5A/6A polymorphism was carried out.


RESULTS
IADE was identified in 12% of stroke patients. There was no association of IADE with mean MMP-2, -3, and -9 plasma levels. After categorization of MMP plasma levels into tertiles, we found a higher risk of IADE with the lowest MMP-3 tertile (adjusted odds ratio [OR], 2.48; 95% confidence interval [CI], 1.17-5.23). In genotype analysis, there was a significant additive effect of the 5A allele on the risk of IADE, with an adjusted OR of 1.62 (95% CI, 1.03-2.55).


CONCLUSIONS
In this cohort of stroke patients of Caucasian ancestry, IADE was associated with low MMP-3 plasma levels and with the 5A/6A polymorphism of the promoter region of MMP-3. These results suggest that MMP-3 may play a role in IADE.
Pico
Fernando
F
Neurology Department, Versailles Hospital and Versailles Saint-Quentin-en-Yvelines University, Versailles, France.
Jacob
Marie-Paule
MP
Labreuche
Julien
J
Soufir
Nadem
N
Touboul
Pierre-Jean
PJ
Benessiano
Joëlle
J
Cambien
François
F
Grandchamp
Bernard
B
Michel
Jean-Baptiste
JB
Amarenco
Pierre
P
D000328:Adult; D000368:Aged; D020520:Brain Infarction / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D002539:Cerebral Arterial Diseases / Q000097:blood* / Q000150:complications / Q000235:genetics*; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9