Elevation of CRABP-I in the Cerebrospinal Fluid of Patients With Moyamoya Disease

Abstract

Background and Purpose-The etiology of moyamoya disease (MMD) remains obscure. This study was undertaken to identify specific proteins associated with the pathogenesis of MMD. Methods-We studied cerebrospinal fluid (CSF) from 20 patients with angiographically confirmed MMD (4 boys and 16 girls; age range, 3 to 13 years; mean, 7.5 years) and 4 control patients with cerebral palsy who underwent selective dorsal rhizotomy (2 boys and 2 girls; age range, 5 to 10 years; mean, 7.3 years). CSF proteins were analyzed by 2-dimensional polyacrylamide gel electrophoresis, and protein identification was performed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry. The presence of specific CSF protein in patients with MMD was confirmed by Western blotting. In addition, cerebral CSF was also tested in 7 patients who had other brain diseases but no MMD (2 boys and 5 girls; age range, 1 to 12 years; mean, 6.9 years). Results-We identified 1 polypeptide spot (M r of 13 to 15 kDa and isoelectric point of 5 to 5.5) that was differentially expressed in the CSF samples of MMD patients (mean optical density intensity, 0.36Ϯ0.24; range, 0.05 to 0.92) and control spinal CSF samples (mean, 0.03Ϯ0.04; range, 0 to 0.08; Pϭ0.002). This polypeptide was identified as cellular retinoic acid-binding protein (CRABP)-I. High levels of expression of CRABP-I in the CSF from 17 MMD children were confirmed by Western blotting. Conclusions-The analysis of the CSF of MMD patients reveals high CRABP-I expression. The present study suggests that the elevation of CRABP-I in CSF may be a candidate for pathogenesis of MMD.

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

“…10,11 Therefore, HGF may be an important specific protein involved in the development of moyamoya disease as well as bFGF, 10,11 soluble adhesion molecules, 12 and CRABP-1. 13 This study revealed that patients with moyamoya disease had significantly higher CSF level of HGF than the controls. Close correlation between CSF level of HGF and onset pattern was observed.…”

“…12 Recently, Kim et al characterized a specific protein, cellular retinoic acid-binding protein-I, from the CSF of patients with moyamoya disease. 13 On the other hand, hepatocyte growth factor (HGF) was discovered as a growth factor of hepatocytes and was subsequently shown to have numerous functions in every tissue. Currently, HGF is also known as a strong inducer of angiogenesis and is more potent than vascular endothelial cell growth factor or bFGF.…”

Endothelial progenitor cells functionally express inward rectifier potassium channels

“…There is interesting evidence suggesting that the transplantation of EPCs enhances in vivo postnatal neovasculogenesis and repairs infarcted myocardium (3,18,19,28,38). Furthermore, the numerical and functional changes in EPCs obtained from patients may be put forth as a criterion for the diagnosis of vascular disease (20,21,34,38).…”

Decreased level and defective function of circulating endothelial progenitor cells in children with moyamoya disease

“…The occlusion of major intracranial arteries is attributed to eccentric fibrocellular thickening of the intima, resulting from the proliferation of smooth muscle cells and fibrosis (Hoshimaru et al, 1991). The pathogenesis of MMD has been speculated on based on the various abnormalities in the affected major intracranial arteries, cerebrospinal fluid proteins and growth factors, including basic fibroblast growth factor (Hoshimaru et al, 1991;Malek et al, 1997), transforming growth factor-b1 (Hojo et al, 1998), platelet-derived growth factor (Aoyagi et al, 1993), and cellular retinoic acidbinding protein-I (Kim et al, 2003), which promotes the migration and proliferation of smooth muscle cells from the media to the intima.…”