Copper chelation represses the vascular response to injury
| Autor: | Michael Simons, Dobroslav Kyurkchiev, Anna Mandinova, Stanimir Kyurkchiev, Volkhard Lindner, Lazar Mandinov, Stephen Bellum, I. Kehayov, Vihren N. Kolev, Raffaella Soldi, Thomas Maciag, Mark J. Post, Cinzia Bagalà, Ebo de Muinck, Igor Prudovsky |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.drug_class Biology Fibroblast growth factor Transfection Peripheral blood mononuclear cell Adenoviridae Rats Sprague-Dawley chemistry.chemical_compound In vivo Extracellular medicine Animals Humans Chelating Agents Molybdenum Multidisciplinary Ceruloplasmin Phosphatidylserine Biological Sciences Receptor antagonist Immunohistochemistry Cell biology Rats chemistry Immunology Blood Vessels Intracellular Copper |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 100(11) |
| ISSN: | 0027-8424 |
| Popis: | The induction of an acute inflammatory response followed by the release of polypeptide cytokines and growth factors from peripheral blood monocytes has been implicated in mediating the response to vascular injury. Because the Cu 2 + -binding proteins IL-1α and fibroblast growth factor 1 are exported into the extracellular compartment in a stress-dependent manner by using intracellular Cu 2 + to facilitate the formation of S100A13 heterotetrameric complexes and these signal peptideless polypeptides have been implicated as regulators of vascular injury in vivo , we examined the ability of Cu 2 + chelation to repress neointimal thickening in response to injury. We observed that the oral administration of the Cu 2 + chelator tetrathiomolybdate was able to reduce neointimal thickening after balloon injury in the rat. Interestingly, although immunohistochemical analysis of control neointimal sections exhibited prominent staining for MAC1, IL-1α, S100A13, and the acidic phospholipid phosphatidylserine, similar sections obtained from tetrathiomolybdate-treated animals did not. Further, adenoviral gene transfer of the IL-1 receptor antagonist during vascular injury also significantly reduced the area of neointimal thickening. Our data suggest that intracellular copper may be involved in mediating the response to injury in vivo by its ability to regulate the stress-induced release of IL-1α by using the nonclassical export mechanism employed by human peripheral blood mononuclear cells in vitro . |
| Databáze: | OpenAIRE |
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