Expression of angiogenesis factors and selected vascular wall matrix proteins in intracranial saccular aneurysms.

Abstract

Little is known about the biological mechanisms associated with the genesis, growth, and rupture of intracranial saccular aneurysms. It is postulated that the vascular wall pathological response of aneurysmal disease is associated with abnormal angiogenesis factor expression. We have examined the expression and distribution of immunoreactivity to angiogenesis growth factors (vascular endothelial growth factor and basic fibroblast growth factor) and selected vascular wall matrix proteins (fibronectin, Type IV collagen, and alpha smooth muscle actin) in the walls of human intracranial aneurysms from surgical biopsy or autopsy specimens. Double antibody immunohistochemical stains were performed in contiguous fixed sections from three control circle of Willis arteries, five berry aneurysms, four giant aneurysms, and one mycotic aneurysm (three unruptured and seven ruptured lesions). The aneurysmal wall exhibited diffuse disorganized expression of matrix proteins as compared to their organization in control vessels. There was strong patchy expression of vascular endothelial growth factor within the walls of all aneurysms, including marked staining of capillaries and small vessels within the thickened walls of giant lesions. The expression of basic fibroblast growth factor was more diffuse and occurred around the fibrocytes and myocytes within the disrupted media of 9 of 10 aneurysms. These results confirm the gross architectural molecular disruption in the walls of intracranial aneurysms and illustrate an apparent biological response involving angiogenesis factors. Further research should elucidate the time course and possible causal relationships of these changes to aneurysm growth and rupture with the aim of possible therapeutic manipulation.