Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 2 Expression in Brain Arteriovenous Malformations and its Association with Brain Arteriovenous Malformation Size

Background and objective: Brain arteriovenous malformations (bAVM) are severe conditions that can cause severe neurologic deficits and mortality. The underlying cellular and molecular mechanisms associated with bAVM growth and rupture remain unclear. The objective of this study was to explore the potential role of PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2) in the pathophysiology of bAVM.

Methods: Expression and localization of PLOD2 were analyzed on tissue microarrays from patients with bAVM (n = 60) by immunohistochemistry. Correlations between PLOD2 levels and clinical parameters were examined with a Pearson test or Spearman rank correlation coefficient. Comparison between different clinical parameters was performed using a t test or nonparametric Mann-Whitney U test. A Fisher exact test was used for categorical data.

Results: PLOD2 was mainly expressed within the tunica media of the blood vessels. High levels of PLOD2 expression correlated with bAVM size (linear regression, P = 0.0083, R²=0.158). Small bAVM showed a higher frequency of hemorrhage compared with large ones (P = 0.001). Although PLOD2 was not directly associated with bAVM hemorrhage, high PLOD2-expressing bAVM had a lower frequency of hemorrhage compared with low or medium PLOD2-expressing bAVM (25% vs. 63% and 75%, respectively).

Conclusions: This study reports for the first time the expression of PLOD2 in bAVM and suggests a potential role of PLOD2 in bAVM pathophysiology. These findings contribute to an better understanding of the microenvironment of bAVM and may foster the development of improved therapeutic strategies for this disease.