Ischemia-induced inflammation in arteriovenous malformations.

The pathophysiology of development, growth, and rupture of arteriovenous malformations (AVMs) is only partially understood. However, inflammation is known to play an essential role in many vascular diseases. This feasibility study was conducted to investigate the expression of enzymes (cyclooxygenase 2 [COX-2] and NLRP3 [NOD-, LRR-, and pyrin domain-containing protein 3]) in the AVM nidus that are essential in their inflammatory pathways and to explore how these influence the pathophysiology of AVMs. The study group comprised 21 patients with partially thrombosed AVMs. The cohort included 8 ruptured and 13 unruptured AVMs, which had all been treated microsurgically. The formaldehyde-fixed and paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 and NLRP3 (COX-2 clone: CX-294; NLRP3: ab214185). The authors correlated MRI and clinical data with immunohistochemistry, using the Trainable Weka Segmentation algorithm for analysis. The median AVM volume was 2240 mm3. The proportion of NLRP3-positive cells was significantly higher (26.23%-83.95%), compared to COX-2 positive cells (0.25%-14.94%, p < 0.0001). Ruptured AVMs had no higher expression of NLRP3 (p = 0.39) or COX-2 (p = 0.44), compared to nonruptured AVMs. Moreover, no patient characteristics could be reported that showed significant correlations to the enzyme expression. NLRP3 consistently showed an approximately 10-fold higher expression level than COX-2, making the inflammatory process in AVMs appear to be mainly associated with ischemic (NLRP3)-driven rather than with mechanical (COX-2)-driven inflammatory pathways. No direct associations between NLRP3 and COX-2 expression and radiological, standard histopathological, or patient characteristics were found in this cohort.