Expression of hypoxia-inducing factor-1 alpha and endoglin in intimal hyperplasia of the middle cerebral artery of patients with Moyamoya disease.
OBJECTIVE
Moyamoya disease (MMD) is a cerebrovascular occlusive disease characterized by progressive stenosis or occlusion at the distal ends of the bilateral internal arteries. In MMD, intimal hyperplasia was previously reported to be found in autopsy samples. In this study focusing on the mechanism of remodeling of the intracranial arterial walls of patients with MMD, we surgically collected tiny pieces of the wall of the middle cerebral artery (MCA) from patients with MMD and analyzed them using histological and immunohistochemical methods.


METHODS
Twelve patients underwent surgical procedures for treatment of standard indications of MMD at Kyoto University Hospital. Specimens of MCA were obtained from MMD patients during the surgical procedures. Nine MCA samples were also obtained in the same way from control patients. The samples were analyzed by immunohistochemical methods.


RESULTS
MCA specimens from MMD patients had a thicker intima than those from the control group. In MMD samples, the immunoreactivity indicating hypoxia-inducing factor-1alpha was higher in the endothelium and intima; endoglin expression was also higher in the endothelium. No vascular endothelial growth factor immunoreactivity was detectable in the MMD samples. In addition, transforming growth factor-beta3 immunoreactivity was also detected and was co-localized with that of hypoxia-inducing factor-1alpha and endoglin, mainly in the endothelium.


CONCLUSIONS
Our results indicate that the MCA specimens from MMD patients had thicker intimal walls than the specimens from control patients. In addition, hypoxia-inducing factor-1alpha and endoglin were overexpressed in the intima of the MCA of MMD patients.
Takagi
Yasushi
Y
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. ytakagi@kuhp.kyoto-u.ac.jp
Kikuta
Ken-Ichiro
K
Nozaki
Kazuhiko
K
Fujimoto
Motoaki
M
Hayashi
Junya
J
Imamura
Hirotoshi
H
Hashimoto
Nobuo
N
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D000071063:Endoglin; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D009072:Moyamoya Disease / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011956:Receptors, Cell Surface