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Plasma matrix metalloproteinases, cytokines and angiogenic factors in moyamoya disease
  1. Hyun-Seung Kang1,
  2. Jin Hyun Kim2,
  3. Ji Hoon Phi1,3,
  4. Young-Yim Kim1,
  5. Jeong Eun Kim1,
  6. Kyu-Chang Wang1,3,
  7. Byung-Kyu Cho1,3,
  8. Seung-Ki Kim1,3
  1. 1Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea
  2. 2Clinical Research Institute, Gyeongsang National University Hospital, Jinju, Gyeongnam, Korea
  3. 3Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, Korea
  1. Correspondence to Dr Seung-Ki Kim, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, 101 Daehangno, Jongno-gu, Seoul, 110-744, Korea; nsthomas{at}


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-1β, IL-6, IL-8), tumour necrosis factor-α, 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-1β, 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.

Conclusion 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.

  • Angiogenic factors
  • moyamoya disease
  • paediatric neurosurgery
  • stroke

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  • Funding This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A080588-8) and by an SBS Grant-in-Aid from the Seoul National University Children's Hospital Research Fund (06-2008-195-9).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by the Seoul National University Hospital Institutional Review Board (#0705-020-208).

  • Provenance and peer review Not commissioned; externally peer reviewed.