Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Clinical significance of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 and 2 in Kawasaki disease

가와사끼병에서 Matrix metalloproteinase 9과 Tissue inhibitor of metalloproteinase 1, 2의 임상적 중요성

  • Yun, Ki-Wook (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Yun, Sin-Weon (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Lee, Jung-Ju (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Chae, Soo-Ahn (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Lim, In-Seok (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Choi, Eung-Sang (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Yoo, Byoung-Hoon (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Lee, Mi-Kyung (Department of Laboratory Medicine, College of Medicine, Chung-Ang University)
  • 윤기욱 (중앙대학교 의과대학 소아과학교실) ;
  • 윤신원 (중앙대학교 의과대학 소아과학교실) ;
  • 이정주 (중앙대학교 의과대학 소아과학교실) ;
  • 채수안 (중앙대학교 의과대학 소아과학교실) ;
  • 임인석 (중앙대학교 의과대학 소아과학교실) ;
  • 최응상 (중앙대학교 의과대학 소아과학교실) ;
  • 유병훈 (중앙대학교 의과대학 소아과학교실) ;
  • 이미경 (중앙대학교 의과대학 진단검사의학과)
  • Received : 2010.01.11
  • Accepted : 2010.03.02
  • Published : 2010.04.15
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Abstract

Purpose : Kawasaki disease (KD) is a systemic vasculitis, a leading cause of pediatric acquired heart disease. Histopathological findings of coronary artery lesion (CAL) in KD indicate destruction of the coronary artery wall with diffuse vasculitis. Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) might play central roles in this process. Special attention to MMP-9 has recently been emerging. This study was performed to investigate the clinical significance of MMP-9 and its inhibitors, TIMP-1 and TIMP-2, in KD. Methods : We compared 47 KD patients with 14 febrile controls. Serum MMP-9 and TIMP-1, TIMP-2 were measured by ELISA and compared according to clinical stages and coronary involvement. Results : In acute stage, MMP-9 and TIMP-1 were significantly higher, whereas TIMP-2 was lower, in KD than those in febrile controls ($P$<0.05). The elevated MMP-9 levels in acute phase significantly decreased during the subacute and convalescent phases ($P$<0.05). During acute phase, the MMP-9, TIMP-1, and MMP-9/TIMP-2 levels in the CAL group were lower than those in the non-CAL group, but they increased significantly in the subacute phase ($P$<0.05). MMP-9 has a positive correlation with TIMP-1 in the acute and subacute phases, and negative correlation with TIMP-2 in the subacute and convalescent phases ($P$<0.05). Conclusion : These results suggest that MMP-9, TIMP-1, and the imbalance in MMP-9 and TIMP-2 might play important roles on the pathophysiology of KD and especially on the development of CAL. However, further larger studies are needed.

목 적: 가와사끼병은 급성 전신성 미세혈관염으로서, 소아의 후천성 심질환의 가장 흔한 원인이다. 가와사끼병의 관상동맥병변에 대한 조직병리학적 소견은 미만성 혈관염에 의한 관상동맥벽의 파괴를 시사하는데, matrix metalloproteinase (MMP)와 그 내인성 억제인자인 tissue inhibitor of metalloproteinases (TIMP)가 이러한 과정에 주요한 역할을 할 것으로 생각되고 있으며, 그 중에도 MMP-9이 최근 가장 주목을 받고 있다. 따라서 본 연구에서는, 한국의 가와사끼병 환아들에서 MMP-9과 그 억제인자들인 TIMP-1, TIMP-2가 갖는 임상적 중요성을 평가하고자 하였다. 방 법: 가와사끼병 환아 47명을 연구대상으로 하였고, 급성열성 세균감염 환아 14명을 대조군으로 하였다. 혈중 MMP-9, TIMP-1, TIMP-2의 농도를 kit를 통한 효소 면역법을 이용하여 측정하였고, 각 임상 단계 및 관상동맥병변의 유무에 따라 비교분석하였다. 결 과: 급성기에 MMP-9과 TIMP-1은 가와사끼군에서 대조군에 비해 유의하게 높았고, TIMP-2는 오히려 낮았다($P$<0.05). 급성기에 증가한 MMP-9은 아급성기와 회복기에 유의하게 감소하였다($P$<0.05). 관상동맥 확장군과 비확장군의 비교에서는, 확장군에서 급성기 MMP-9과 TIMP-1, MMP-9/TIMP-2가 낮았으며, 아급성기로 가면서 통계적으로 유의하게 증가하였다가 다시 회복기로 가면서 감소하는 양상을 보였다($P$<0.05). MMP-9은 급성기와 아급성기에 TIMP-1과 통계적으로 유의한 양의 상관관계를 보였고, TIMP-2와는 아급성기와 회복기에 음의 상관관계를 보였다($P$<0.05). 결 론: 이러한 결과들은 MMP-9과 TIMP-1의 증가, 그리고 MMP-9과 TIMP-2의 불균형이 가와사끼병, 특히 그 관상동맥병변의 병태생리에 핵심적인 역할을 한다는 사실을 시사한다 하겠다. 더 종합적이고 심도 깊은 연구를 위해서 좀 더 많은 대상자를 포함하는 큰 규모의 연구들이 향후 이루어져야 할 것이다.

Keywords

References

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