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      The proteoglycan osteoglycin/mimecan is correlated with arteriogenesis

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          Abstract

          Arteriogenesis or collateral growth is able to compensate for the stenosis of major arteries. Using differential display RT-PCR on growing and quiescent collateral arteries in a rabbit femoral artery ligation model, we cloned the rabbit full-length cDNA of osteoglycin/mimecan. Osteoglycin was present in the adventitia of collateral arteries as a glycosylated protein without keratan sulfate side chains, mainly produced by smooth muscle cells (SMCs) and perivascular fibroblasts. Northern blot, Western blot, and immunohistochemistry confirmed a collateral artery-specific downregulation of osteoglycin from 6 h to 3 weeks after the onset of arteriogenesis. Treatment of primary SMCs with the arteriogenic protein fibroblast growth factor-2 (FGF-2) resulted in a similar reduction of osteoglycin expression as observed in vivo. Application of the FGF-2 inhibitor polyanethole sulfonic acid (PAS) blocked the downregulation of osteoglycin and interfered with arteriogenesis. From our study we conclude that downregulation of osteoglycin is a fundamental requirement for proper arteriogenesis.

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          Most cited references34

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          Molecular Cloning : A Laboratory Manual

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            Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction

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              Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb.

              We have previously shown that monocytes adhere to the vascular wall during collateral vessel growth (arteriogenesis) and capillary sprouting (angiogenesis). In this study we investigated the association of monocyte accumulation with both the production of the cytokines-basic fibroblast growth factor (bFGF) and TNF-alpha-and vessel proliferation in the rabbit after femoral artery occlusion. In particular, we studied the effects of an increase in monocyte recruitment by LPS on capillary density as well as collateral and peripheral conductance after 7 d of occlusion. Monocytes accumulated around day 3 in collateral arteries when maximal proliferation was observed, and stained strongly for bFGF and TNF-alpha. In the lower limb where angiogenesis was shown to be predominant, macrophage accumulation was also closely associated with maximal proliferation (around day 7). LPS treatment significantly increased capillary density (424+/-26.1 n/mm2 vs. 312+/-20.7 n/mm2; P < 0.05) and peripheral conductance (109+/-33.8 ml/min/100 mmHg vs. 45+/-6.8 ml/min/100 mmHg; P < 0.05) as compared with untreated animals after 7 d of occlusion. These results indicate that monocyte activation plays a major role in angiogenesis and collateral artery growth.
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                Author and article information

                Contributors
                +49-6032-705311 , +49-6032-705211 , rene.zimmermann@mpi-bn.mpg.de
                Journal
                Mol Cell Biochem
                Molecular and Cellular Biochemistry
                Springer US (Boston )
                0300-8177
                1573-4919
                4 November 2008
                February 2009
                : 322
                : 1-2
                : 15-23
                Affiliations
                [1 ]Research Group Vascular Genomics, Kerckhoff Clinic, Bad Nauheim, Germany
                [2 ]Department of Animal Biology, Faculty of Science, University of Málaga, Malaga, Spain
                [3 ]Walter-Brendel-Center for Experimental Medicine, LMU Muenchen, Munich, Germany
                [4 ]Department of Development and Remodeling of the Heart, Max-Planck-Institute for Heart and Lung Research, Parkstrasse 1, 61231 Bad Nauheim, Germany
                [5 ]Arteriogenesis Research Group, Max Planck Institute, Bad Nauheim, Germany
                [6 ]Institute of Toxicology, Merck KGaA, Darmstadt, Germany
                [7 ]University Medical Center, Utrecht, The Netherlands
                Article
                9935
                10.1007/s11010-008-9935-x
                2758385
                18979232
                7ec85f13-d32f-471b-9f5b-7f1305945ad8
                © Springer Science+Business Media, LLC. 2008
                History
                : 12 August 2008
                : 13 October 2008
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media, LLC. 2009

                Biochemistry
                smooth muscle cells,collateral arteries,differential display,gene expression,proteoglycans,fibroblast growth factor-2

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