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Elevated circulating levels of matrix metalloproteinases MMP-2 and MMP-9 in pseudoxanthoma elasticum patients

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Abstract

Pseudoxanthoma elasticum (PXE) is a rare disorder predominantly affecting the skin, the eyes, and the cardiovascular system. The disease is caused by mutations in the ABCC6 gene and characterized by ectopic calcification and extracellular matrix (ECM) alterations. Matrix metalloproteinases (MMPs) play a pivotal role in the process of ECM remodeling. In the present study, we investigated matrix metalloproteinases MMP-2 and MMP-9 in PXE patients compared to healthy controls. We analyzed the serum concentrations of MMP-2 and MMP-9 in a cohort of 69 German PXE patients and in 69 healthy, age-, and sex-matched control subjects using commercially available ELISA assays. We found elevated concentrations of both MMPs in the sera of PXE patients. MMP-2 levels were significantly higher in patients than controls (231 ± 5.89 vs 202 ± 5.17 ng/ml, p = 0.0002), as were MMP-9 levels (841 ± 65.9 vs 350 ± 30.8 ng/ml, p < 0.0001). Our findings point to an involvement of matrix metalloproteinases in PXE pathology. ECM remodeling in PXE is reflected by elevated levels of circulating MMP-2 and MMP-9. Those MMPs might, therefore, be applicable as serum markers for the matrix-degradative process in PXE.

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Acknowledgments

We wish to thank Christoph Lichtenberg and Marlen Ewald for their excellent technical assistance and Sarah L. Kirkby for her linguistic advice. We are very grateful to all the PXE patients and their relatives, whose cooperation made this study possible. Furthermore, we thank Peter Hof, chairman of the Selbsthilfegruppe für PXE-Erkrankte Deutschlands 1999 e.V., and the members of the Clinical Outpatients Department for PXE at the Bethesda Hospital in Freudenberg, Germany.

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Authors and Affiliations

  1. Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Georgstraße 11, 32545, Bad Oeynhausen, Germany

    Ulf Diekmann, Ralf Zarbock, Doris Hendig, Knut Kleesiek & Christian Götting

  2. Dermatologische Klinik, Krankenhaus Bethesda, 57258, Freudenberg, Germany

    Christiane Szliska

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  1. Ulf Diekmann
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  2. Ralf Zarbock
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  6. Christian Götting
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Correspondence to Christian Götting.

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Diekmann, U., Zarbock, R., Hendig, D. et al. Elevated circulating levels of matrix metalloproteinases MMP-2 and MMP-9 in pseudoxanthoma elasticum patients. J Mol Med 87, 965–970 (2009). https://doi.org/10.1007/s00109-009-0497-5

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  • DOI: https://doi.org/10.1007/s00109-009-0497-5

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