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Brain arteriovenous malformations (bAVM) are rare vascular lesions. Recent observations challenge the congenital nature of these lesions. The underlying cellular and molecular mechanisms associated with dynamic changes of bAVM still remain unclear. The objective of this study was to explore the potential role of COL4A2 (Collagen alpha-2(IV)) in the pathophysiology of bAVM. Expression and localization of COL4A2 were analyzed on tissue microarrays from bAVM patients (n = 60) by immunohistochemistry. Correlations between COL4A2 levels and clinical parameters were examined with Pearson's test for normally- distibuted or Spearman's Rho for not normally distributed data. Comparison between different clinical parameters was performed using t-test, non-parametric Mann-Whitney U test or Kruskal- Wallis test. Fisher's exact test was used for categorical data. COL4A2 was mainly expressed beneath the endothelium of vessels in the tunica media of bAVM. This pattern of expression indicates the basement membrane of the vessel walls. High levels of COL4A2 expression correlated with the age at surgery of patients (p = 0.005; R = 0.393; Spearman's Rho). The age at surgery in young (17-25 years) and old patients (55-76 years) showed a linear correlation; a greater variance of COL4A2 expression was observed in the age group between 26-54 years. This study reports for the first time the expression of COL4A2 in bAVM and suggests a potential role of COL4A2 in bAVM pathophysiology. These findings contribute to a better understanding of the microenvironment of bAVM and may foster the development of improved therapeutic strategies for this disease. Copyright © 2019. Published by Elsevier B.V.


Belal Neyazi, Klaus-Peter Stein, Ludwig Wilkens, Homajoun Maslehaty, Claudia A Dumitru, I Erol Sandalcioglu. Age-dependent changes of collagen alpha-2(IV) expression in the extracellular matrix of brain arteriovenous malformations. Clinical neurology and neurosurgery. 2020 Feb;189:105589

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PMID: 31837516

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