Proliferative activity through extracellular signal-regulated kinase of smooth muscle cells in vascular walls of cerebral arteriovenous malformations.
OBJECTIVE
We examined the expression and localization of phosphorylated extracellular signal-regulated kinase (pERK) and proliferation-related antigens in human cerebral arteriovenous malformations (AVMs) to clarify the role of vascular remodeling via this pathway in the development of the lesions.


METHODS
Thirteen cerebral AVMs and five control specimens were analyzed using immunohistochemical methods. Specimens were obtained from the patients during the surgical procedures. Control middle cerebral artery samples were obtained during autopsies.


RESULTS
We performed immunohistochemical analysis of AVMs by using an antibody specifically recognizing pERK. pERK immunoreactivity was detected in all specimens. Among the control specimens, only weak pERK immunoreactivity was detected, mainly in the intima. pERK immunoreactivity was located in nuclei of cells in the endothelial layer and media. Semiquantitative analysis for pERK immunoreactivity showed that the immunoreactivity score in the media was significantly higher for the AVM than for the control specimens. The results of double staining for pERK and proliferating cell nuclear antigen indicated that these immunoreactivities were colocalized in the same cells. Moreover, those cells in the media were immunoreactive for alpha-actin, indicating that they were smooth muscle cells.


CONCLUSIONS
pERK was detected in smooth muscle cells of the vascular walls of AVMs. It may function in the proliferative activity of smooth muscle cells. Vascular remodeling through pERK may play an important role in the growth and maintenance of cerebral vascular malformations.
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ytakagi@kuhp.kyoto-u.ac.jp
Yasushi
Y
Takagi
Ken-Ichiro
K
Kikuta
Nobutake
N
Sadamasa
Kazuhiko
K
Nozaki
Nobuo
N
Hashimoto
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D002648:Child; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000201:enzymology*
D048049:Extracellular Signal-Regulated MAP Kinases