Growth factor receptor expression and remodeling of saccular cerebral artery aneurysm walls: implications for biological therapy preventing rupture.
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.


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).


CONCLUSIONS
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.
Frösen
Juhana
J
Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland. juhana.frosen@hus.fi
Piippo
Anna
A
Paetau
Anders
A
Kangasniemi
Marko
M
Niemelä
Mika
M
Hernesniemi
Juha
J
Jääskeläinen
Juha
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D017542:Aneurysm, Ruptured / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D001691:Biological Therapy / Q000379:methods*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D002532:Intracranial Aneurysm / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008866:Microsurgery; D008875:Middle Aged; D017978:Receptors, Growth Factor / Q000032:analysis / Q000096:biosynthesis*
D017978:Receptors, Growth Factor