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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 Phi3,
  4. Young-Yim Kim1,
  5. Jeong Eun Kim1,
  6. Kyu-Chang Wang4,
  7. Byung-Kyu Cho4,
  8. Seung-Ki Kim4,*
  1. 1 Seoul National University College of Medicine, Korea, Republic of;
  2. 2 Gyeongsang National University Hospital, Korea, Republic of;
  3. 3 Seoul National University Children HospitalSeoul National University Children¡¯s Hospital, Korea, Republic of;
  4. 4 Seoul National University Children¡¯s Hospital, Korea, Republic of
  1. Correspondence to: , ; 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 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), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), and basic fibroblast growth factor (bFGF) was determined using multianalyte profiling systems. The concentration of the tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2) was measured using enzyme-linked immunosorbent assay. 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.

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