2002 Fiscal Year Final Research Report Summary
Role of Matrix Metalloproteinase in Vascular Remodeling
| Project/Area Number |
13671182
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Nagoya University |
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Principal Investigator |
KUZUYA Masafumi Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10283441)
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| Co-Investigator(Kenkyū-buntansha) |
KANDA Shigeru Nagoya University, University Hospital, Medical staff, 医学部附属病院, 医員
IGUCHI Akihisa Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20109763)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Matrix Metallouroteinase / Intimal hyperplasia / vascular smooth muscle cell / MMP-2-null mutant mice |
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| Research Abstract |
Background
Although it has been demonstrated that matrix metalloproteinases (MMPs) play an important role in the arterial remodeling in atherosclerosis and restenosis, it is not clear which MMP is involved in which process. To define the role of MMP-2 in arterial remodeling, we evaluated the influence of the targeted deletion of the MMP-2 gene on vascular remodeling after flow cessation in the murine carotid arteries.
Methods and Results
The left common carotid arteries of wild-type and MMP-2-deficient mice were ligated just proximal to their bifurcations, and the animals were then processed for morphological and biochemical studies at specific time points. MMP-2 activity and mRNA levels increased in ligated carotid arteries of wild-type mice on the basis of observation by gelatin zymography and quantitative real-time RT-PCR. There was significantly less intimal hyperplasia in MMP-2-deficient mice at 2 and 4 weeks after ligation than there in wild-type mice. Arterial explants from the aorta of MMP-2-deficient mice showed that smooth muscle cell (SMC) migration was inhibited in comparison with wild-type mice. The chemoattractant-directed invasion through a reconstituted basement membrane barrier was significantly reduced in cultured SMCs derived from MMP-2-deficient mice, although no difference was observed in SMC migration across the filter or in proliferative response between the control and MMP-2-deficient mice.
Conclusions
In a mouse carotid artery blood flow cessation model, MMP-2 contributes to intimal hyperplasia mainly through the SMC migration from the media into the intima by degrading and breaching the extracellular matrix proteins surrounding each cell and the basement membrane barrier.
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Research Products
(26 results)
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[Publications] Shi G-P, Sukhova GK, Kuzuya M, Ye Q, Du J, Zhang Y, Pan J-H, Lu M, Cheng XW, Iguchi A, Perrey S, Lee AM-E, Libby P: "Deficiency of the cysteine protease cathepsin S impairs microvessel growth"Cir Res. in press. (2003)
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[Publications] Kuzuya M, Suzuki Y, Asai T, Koike T, Kanda S, Nakamura A, Satake S,Umegaki H, Iguchi A: "Atorvastatin, HMG-CoA reductase inhibitor, reduces bone resorption in the elderly"J Am Ger Soc. in press. (2003)
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[Publications] Kuzuya,M., Asai,T., Kanda,S., Maeda,K., Cheng,XW., Iguchi,A: "Glycation cross-links inhibit matrix metalloproteinase-2 activation in vascular smooth muscle cells cultured on collagen lattice"Diabetologia. 44. 433-436 (2001)
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