복부대동맥류 환자의 대동맥 조직에서 기질 단백분해효소와 내인성 억제물질의 발현
Expression of Matrix Metalloproteinases and Their Endogenous Inhibitors in Human Abdominal Aortic Aneurysms
정인묵, 정중기, 민승기, 서정욱, 박재형, 하종원, 김상준,
소속 상세정보
정인묵 ( Jung In-Mok )
서울대학교 의과대학 보라매병원 외과
정중기 ( Chung Jung-Kee )
서울대학교 의과대학 보라매병원 외과
민승기 ( Min Seung-Kee )
가천의과학대학교 외과학교실
서정욱 ( Seo Jeong-Wook )
서울대학교 의과대학 병리학교실
박재형 ( Park Jea-Hyung )
서울대학교 의과대학 방사선과학교실
하종원 ( Ha Jong-Won )
서울대학교 의과대학 외과학교실
김상준 ( Kim Sang-Joon )
서울대학교 의과대학 외과학교실
KMID : 0371320040670030214
Abstract
PURPOSE: Among the theories in the pathogenesis of abdominal aortic aneurysms, matrix metalloproteinase (MMP)- induced excessive degradation of extracellular matrix protein has been widely recognized. Normally, MMPs keep a balance with their endogenous tissue inhibitors of metalloproteinases (TIMPs). Recently, the MMP-TIMP imbalance has been investigated for potential etiological role in AAA formation. The aim of this study was to define the role of the imbalance between the expressions of the specific MMPs and their physiologic inhibitors (TIMPs) in the formation of human abdominal aortic aneurysm (AAA).
METHODS: Aortic tissues from 12 patients with AAAs, 4 age-matched patients with aortoiliac occlusive diseases (AODs), and 6 cadaveric organ donors, as normal controls, were obtained and prepared. The productions and expressions of MMP-2, 9, MT1-MMP and TIMP-1, 2, and 4 were analyzed using gelatin zymography, Western blotting, and immunohistochemistry.
RESULTS: In the gelatin zymography, the net matrix-degrading activities were higher in the AAAs and AODs than in the normal control group due to the higher presence of MMP-2 and 9. From the Western blot analysis and immunohistochemistry, those with AAAs and AODs showed significantly higher expressions of MMP-2, 9, and MT1-MMP than the normal control group. However, no differences in the TIMP-1 and 2 expressions were found between the all groups. In contrast, TIMP-4 protein was expressed at a significantly lower level in the AAAs and AODs than in the normal control group. MMP-9/TIMP-1, MMP-2/TIMP-2, and MMP-2/TIMP-4 were significantly different between AAAs and normal control group. From the densitometric analysis of the Western blotting, no significant differences were found in tissue expressions of MMPs and TIMPs between the AAAs and AODs groups, but, in the immunohistochemistry, the AAAs group showed a different distribution of the MMP expression confined to sites of overt medial damage compared with that in the intimal plaque in AODs.
CONCLUSION: The imbalance of expression between specific MMPs and their endogenous inhibitors plays an etiological role in the formation of AAAs. In addition, TIMP-4 may suppress the MMP-induced aneurysmal formation. Our results suggest that the eventual formation of aneurysms or occlusive lesions appears not to result from an ongoing difference in the proteolytic activities, but from differences in other factors, as-yet-undefined, including the distribution of MMPs expression within the aortic walls.
키워드
기질 단백분해 효소;기질 단백분해 억제효소;복부대동맥류;대동맥-장골동맥 폐색성 질환;Matrix metalloproteinases;Tissue inhibitors of metalloproteinases;Abdominal aortic aneurysm;Aortoiliac occlusive disease
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