Plasma matrix metalloproteinases, cytokines and angiogenic factors in moyamoya disease.
OBJECTIVE
To document the expression patterns of various matrixins, cytokines and angiogenic factors in plasma to assess their involvement in the pathogenesis of moyamoya disease (MMD).


METHODS
This study included plasma samples from 20 MMD patients and nine healthy individuals. The plasma concentration of five matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9, MMP-12), monocyte chemoattractant protein-1 (MCP-1), resistin, three interleukins (IL-1beta, IL-6, IL-8), tumour necrosis factor-alpha, vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB) and basic fibroblast growth factor was determined using multianalyte profiling systems. The concentration of the tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2) was measured using ELISA. Gelatin zymography for MMP-2 and MMP-9 was also performed.


RESULTS
MMD patients exhibited significantly higher plasma concentrations of MMP-9, MCP-1, IL-1beta, VEGF and PDGF-BB, and lower plasma concentrations of MMP-3, TIMP-1 and TIMP-2 compared with healthy controls. Significant correlations were found among MMP-9, MCP-1, VEGF, PDGF-BB and TIMP-2 in MMD patients.


CONCLUSIONS
There were distinctive expression patterns of matrixins, cytokines and angiogenic factors in MMD patients, which seemed to correlate with disease pathogenesis. The balance between MMPs and TIMPs was disrupted in MMD and correlated with disease pathogenesis. Increased plasma levels of MCP-1 and VEGF in MMD patients may play a role in the recruitment of vascular progenitor cells and in the formation of collateral vessels.
Kang
Hyun-Seung
HS
Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.
Kim
Jin Hyun
JH
Phi
Ji Hoon
JH
Kim
Young-Yim
YY
Kim
Jeong Eun
JE
Wang
Kyu-Chang
KC
Cho
Byung-Kyu
BK
Kim
Seung-Ki
SK
D000328:Adult; D014408:Biomarkers, Tumor; D016207:Cytokines / Q000097:blood*; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008222:Lymphokines / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D009072:Moyamoya Disease / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D042442:Vascular Endothelial Growth Factors / Q000097:blood*
D014408:Biomarkers, Tumor; D016207:Cytokines; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D020782:Matrix Metalloproteinases