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Up-regulation of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase were coupled with that of type I procollagen in granulation tissue response after the onset of aortic dissection

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Abstract

The pathophysiological significance of matrix metalloproteinases (MMPs) in aortic dissection remains poorly understood. The purpose of the present study is to clarify the significance of MMPs in aortic dissection. The activities and distributions of MMP-2, membrane-type 1-MMP (MT1-MMP), and MMP-9 were evaluated by gelatin zymography, immunohistochemistry, and in situ hybridization in 29 patients and seven autopsy cases. To assess if these MMPs are related to a tissue remodeling process, we compared the expression of these MMPs with that of type I procollagen and platelet-derived growth factor receptor β chain (PDGF Rβ). Patients were divided into three groups based on histological findings: acute, intermediate, and healed groups. The most remarkable changes were observed in the intermediate group, in which MMP-2 activity peaked and tissue expression of mRNAs for MMP-2 and MT1-MMP were observed in spindle-shaped cells in the neointima, organizing thrombus, and the adventitia. These expression patterns were essentially coupled with those of type I procollagen mRNA and PDGF-Rβ protein. The association of MMP-2, MT1-MMP, type I procollagen, and PDGF-Rβ suggests that MMP-2 and MT1-MMP could be involved not only in the degradation of aortic tissue but also in tissue remodeling, which may be associated with the healing process.

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Acknowledgements

We are grateful to Dr. Kazuhiko Igarashi (Department of Biomedical Chemistry, Hiroshima University School of Medicine) for his help with the molecular biological techniques, and to Dr. Shoko Miura and Dr. Isao Ohno (Department of Infectious and Respiratory Diseases, Tohoku University Graduate School of Medicine) for their technical guidance on gelatin zymography. Technical assistance from Ms. Fumiko Date is greatly appreciated. The present study was supported by the Japan Foundation of Cardiovascular Research from 2000 to 2002.

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Correspondence to Masatoshi Akiyama.

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Akiyama, M., Ohtani, H., Sato, E. et al. Up-regulation of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase were coupled with that of type I procollagen in granulation tissue response after the onset of aortic dissection. Virchows Arch 448, 811–821 (2006). https://doi.org/10.1007/s00428-006-0194-5

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