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Matrix metalloproteinase-3 and intracranial arterial dolichoectasia

Authors

  • Fernando Pico MD, PhD,

    1. Neurology Department and Stroke Center, Versailles Hospital and Versailles Saint-Quentin-en-Yvelines University, Versailles, Paris, France
    2. INSERM 698, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
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  • Marie-Paule Jacob PhD,

    1. INSERM 698, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
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  • Julien Labreuche BS,

    1. INSERM 698, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
    2. Department of Neurology and Stroke Center, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
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  • Nadem Soufir MD, PhD,

    1. Department of Biochemistry and Genetics, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
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  • Pierre-Jean Touboul MD,

    1. INSERM 698, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
    2. Department of Neurology and Stroke Center, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
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  • Joëlle Benessiano PhD,

    1. Department of Biochemistry and Genetics, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
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  • François Cambien MD,

    1. INSERM U-525, Pierre and Marie Curie University, Paris, France
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  • Bernard Grandchamp MD, PhD,

    1. Department of Biochemistry and Genetics, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
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  • Jean-Baptiste Michel MD, PhD,

    1. INSERM 698, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
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  • Pierre Amarenco MD

    Corresponding author
    1. INSERM 698, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
    2. Department of Neurology and Stroke Center, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France
    • Department of Neurology and Stroke Center, Bichat University Hospital, 46 rue Henri Huchard, 75018 Paris, France
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Abstract

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).

Interpretation

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. ANN NEUROL 2010;67:508–515

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