Growth Factor Receptor Expression and Remodeling of Saccular Cerebral Artery Aneurysm Walls: Implications for Biological Therapy Preventing Rupture

Abstract

OBJECTIVE: Remodeling of the saccular cerebral artery aneurysm (SCAA) wall, known to be associated with rupture, might be modified with bioactive endovascular implants or systemic drug therapy targeted at growth factor receptors to prevent rupture. The receptors regulating SCAA wall remodeling are, however, unknown. MATERIALS AND METHODS: Immunostaining for 12 growth factor receptors, and markers for matrix synthesis, proliferation, and inflammatory cell infiltration, were analyzed in 21 unruptured and 35 ruptured aneurysm fundi resected after microsurgical clipping of the aneurysm neck. The results were compared with clinical and radiological data. RESULTS: Eleven of the 12 receptors studied were expressed at varying intensities in the 56 SCAA walls. Only transforming growth factor (TGF)beta-R2 and vascular endothelial growth factor (VEGF)-R1 were associated with rupture and basic fibroblast growth factor-R1 with minor leaks (P = 0.018). TGFbeta-R3 and VEGF-R1 was associated with wall remodeling (P = 0.043 and 0.027), and VEGF-R1 was associated with T-cell and macrophage infiltration as well as organization of luminal thrombosis (P = 0.019). VEGF-R2 was associated with myointimal hyperplasia (P = 0.017) and proliferation (P < 0.001). CONCLUSION: VEGF, TGFbeta, and basic fibroblast growth factor receptors were associated with SCAA wall remodeling, making them potential targets for bioactive endovascular implants or drug therapy aiming to reinforce the SCAA wall.