Increased Expression of Hepatocyte Growth Factor in Cerebrospinal Fluid and Intracranial Artery in Moyamoya Disease

Abstract

Background and Purpose— The etiology of moyamoya disease still remains unknown. This study was aimed to explore the role of hepatocyte growth factor (HGF), a strong inducer of angiogenesis, in development of moyamoya disease. Methods— We studied cerebrospinal fluid (CSF) from 39 patients with moyamoya disease (24 children and 15 adults), 6 control patients with cervical spondylosis, and 7 control patients with internal carotid artery occlusion. CSF level of HGF was determined by enzyme-linked immunosorbent assay technique. We also evaluated the distribution of HGF and its cellular receptor c-Met in the carotid fork obtained from 2 patients with moyamoya disease and 2 control patients. Results— CSF level of HGF was 408.2±201.6 pg/mL and 443.2±193.5 pg/mL in patients with cervical spondylosis and internal carotid artery occlusion, respectively (mean±SD). On the other hand, CSF level of HGF was 820.3±319.0 pg/mL in patients with moyamoya disease, being significantly higher than those in 2 control groups ( P <0.01). Both HGF and c-Met were widely distributed in the media and thickened intima of the carotid fork in patients with moyamoya disease but not in control patients. Conclusions— This study revealed that HGF is densely found in the carotid fork, and its CSF level is markedly elevated in moyamoya disease, suggesting that HGF may be a key protein for pathogenesis of moyamoya disease.

Circulating Endothelial Progenitor Cells as a Pathogenetic Marker of Moyamoya Disease

“…The pathophysiology of MMD has not been elucidated, but major intracranial arteries are known to be occluded by eccentric fibrocellular intimal thickening because of smooth muscle cell proliferation and fibrosis (Yamashita et al, 1983;Masuda et al, 1993). Moreover, collateral pathways, that is, fine-vessel networks (moyamoya vessels) and transdural anastomoses develop because of intimal proliferation (angiogenesis) or recruitment of EPCs (vasculogenesis) (Hoshimaru et al, 1991;Nanba et al, 2004;Yoshimoto et al, 1996). In the present study, CFU numbers and outgrowth cell yields were used to identify EPCs in blood.…”

“…Although the exact cellular and/or paracrine mechanisms involved in EPC-mobilization, recruitment, and homing are unclear, this regenerative process appears to be regulated by a variety of chemokines and cytokines (Hristov et al, 2003). In terms of growth factors and cytokines in MMD, the vascular endothelial growth factor, fibroblast growth factor, hepatocyte growth factor, and plateletderived growth factor have been reported to increase in the cerebrospinal fluid and dural tissue in MMD patients (Hoshimaru et al, 1991;Aoyagi et al, 1996;Yoshimoto et al, 1996;Soriano et al, 2002;Kim et al, 2003;Nanba et al, 2004;Sakamoto et al, 2008). Another analysis of the cerebrospinal fluid from MMD patients revealed high levels of cellular retinoic acid-binding protein-I expression, which is known to enhance the expressions of growth factors (Kim et al, 2003).…”

Moyamoya Disease Is Associated With Endothelial Activity Detected by Anti-Nestin Antibody

“…Abnormalities in caspase-3 expression in vessel wall have been described as well as increased expression of hepatocyte growth factor (HGF) and its receptor c-Met in the media and thickened intima 11,12 . The latter suggest that enhanced expression of HGF in the arterial smooth muscle cells might promote thickening of the intima and encourage migration of the muscle cells into the intima.…”

Enfermedad de Moyamoya: reporte de un caso.

“…Por otra parte, diversos reportes de pacientes con EMM han mostrado niveles elevados en suero y/o líquido cefalorraquídeo de factores de crecimiento como el factor de crecimiento de fibroblastos, el factor de crecimiento transformante beta (TGF-β1), el factor de crecimiento de hepatocitos, etc. ; y otros péptidos como lasmetaloproteinasas de la matriz (MMP-9), las moléculas de adhesión intracelular y el factor inducible por hipoxia 1α (12,13), los cuales contribuirían con el desarrollo de las alteraciones histológicas propias de la enfermedad (14).En nuestro paciente no se realizó ni el análisis genético ni la detección de los biomarcadores debido a que en su mayoría no están disponibles en el país.…”