gms | German Medical Science

Objective: Cerebral arteriovenous malformations (bAVM) are rare vascular lesions. Recent observations challenge the invariable structure of these lesions. The underlying cellular and molecular mechanisms associated with dynamic changes of bAVM still remain unclear. Recent studies emphasize a potential contribution of the ECM to the pathophysiology of bAVM. Here we present the potential role of three proteins which are essentially involved in the configuration of the ECM of bAVM: PLOD2, COL4A2 and DYNLT1.

Methods: Expression and localization of PLOD2, COL4A2 and DYNLT1 were analyzed on tissue microarrays from bAVM patients (n=60) by immunohistochemistry. Correlations between PLOD2, COL4A2 and DYNLT1 levels and clinical parameters were examined with Pearson’s test or Spearman’s rank correlation coefficient. Comparison between different clinical parameters was performed using t-test or non-parametric Mann-Whitney U-test. Fisher’s exact test was used for categorical data.

Results: PLOD2 and DYNLT1 were mainly expressed within the tunica media of the blood vessels. The expression pattern of COL4A2 beneath the endothelium of vessels indicated the basement membrane of vessel walls. High levels of COL4A2 expression correlated with the age at surgery of patients (p=0.005; R=0.393; Spearman’s Rho). Both PLOD2 and DYNLT1 correlated with the size of bAVM (p=0.008, R²=0.158 and p=0.003, R²=0.410, linear regression). Furthermore, within the ruptured bAVM group, DYNLT1 showed a peak of expression in patients who underwent surgery 24–72h after hemorrhage (p=0.031, Kruskal-Wallis).

Conclusion: Our findings substantiate the role of the ECM in the pathophysiology of bAVM and may foster a better understanding of this disease beyond descriptive analyses.