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Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo
Stromelysin-3 is an unusual matrix metalloproteinase, being released in the active rather than zymogen form and having a distinct substrate specificity, targeting serine proteinase inhibitors (serpins), which regulate cellular functions involved in atherosclerosis. We report here that human atherosc...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1999
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192948/ https://www.ncbi.nlm.nih.gov/pubmed/10049948 |
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author | Schönbeck, Uwe Mach, François Sukhova, Galina K. Atkinson, Elizabeth Levesque, Ethan Herman, Michael Graber, Pierre Basset, Paul Libby, Peter |
author_facet | Schönbeck, Uwe Mach, François Sukhova, Galina K. Atkinson, Elizabeth Levesque, Ethan Herman, Michael Graber, Pierre Basset, Paul Libby, Peter |
author_sort | Schönbeck, Uwe |
collection | PubMed |
description | Stromelysin-3 is an unusual matrix metalloproteinase, being released in the active rather than zymogen form and having a distinct substrate specificity, targeting serine proteinase inhibitors (serpins), which regulate cellular functions involved in atherosclerosis. We report here that human atherosclerotic plaques (n = 7) express stromelysin-3 in situ, whereas fatty streaks (n = 5) and normal arterial specimens (n = 5) contain little or no stromelysin-3. Stromelysin-3 mRNA and protein colocalized with endothelial cells, smooth muscle cells, and macrophages within the lesion. In vitro, usual inducers of matrix metalloproteinases such as interleukin-1, interferon-γ, or tumor necrosis factor α did not augment stromelysin-3 in vascular wall cells. However, T cell–derived as well as recombinant CD40 ligand (CD40L, CD154), an inflammatory mediator recently localized in atheroma, induced de novo synthesis of stromelysin-3. In addition, stromelysin-3 mRNA and protein colocalized with CD40L and CD40 within atheroma. In accordance with the in situ and in vitro data obtained with human material, interruption of the CD40–CD40L signaling pathway in low density lipoprotein receptor–deficient hyperlipidemic mice substantially decreased expression of the enzyme within atherosclerotic plaques. These observations establish the expression of the unusual matrix metalloproteinase stromelysin-3 in human atherosclerotic lesions and implicate CD40–CD40L signaling in its regulation, thus providing a possible new pathway that triggers complications within atherosclerotic lesions. |
format | Text |
id | pubmed-2192948 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21929482008-04-16 Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo Schönbeck, Uwe Mach, François Sukhova, Galina K. Atkinson, Elizabeth Levesque, Ethan Herman, Michael Graber, Pierre Basset, Paul Libby, Peter J Exp Med Articles Stromelysin-3 is an unusual matrix metalloproteinase, being released in the active rather than zymogen form and having a distinct substrate specificity, targeting serine proteinase inhibitors (serpins), which regulate cellular functions involved in atherosclerosis. We report here that human atherosclerotic plaques (n = 7) express stromelysin-3 in situ, whereas fatty streaks (n = 5) and normal arterial specimens (n = 5) contain little or no stromelysin-3. Stromelysin-3 mRNA and protein colocalized with endothelial cells, smooth muscle cells, and macrophages within the lesion. In vitro, usual inducers of matrix metalloproteinases such as interleukin-1, interferon-γ, or tumor necrosis factor α did not augment stromelysin-3 in vascular wall cells. However, T cell–derived as well as recombinant CD40 ligand (CD40L, CD154), an inflammatory mediator recently localized in atheroma, induced de novo synthesis of stromelysin-3. In addition, stromelysin-3 mRNA and protein colocalized with CD40L and CD40 within atheroma. In accordance with the in situ and in vitro data obtained with human material, interruption of the CD40–CD40L signaling pathway in low density lipoprotein receptor–deficient hyperlipidemic mice substantially decreased expression of the enzyme within atherosclerotic plaques. These observations establish the expression of the unusual matrix metalloproteinase stromelysin-3 in human atherosclerotic lesions and implicate CD40–CD40L signaling in its regulation, thus providing a possible new pathway that triggers complications within atherosclerotic lesions. The Rockefeller University Press 1999-03-01 /pmc/articles/PMC2192948/ /pubmed/10049948 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Schönbeck, Uwe Mach, François Sukhova, Galina K. Atkinson, Elizabeth Levesque, Ethan Herman, Michael Graber, Pierre Basset, Paul Libby, Peter Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo |
title | Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo |
title_full | Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo |
title_fullStr | Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo |
title_full_unstemmed | Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo |
title_short | Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo |
title_sort | expression of stromelysin-3 in atherosclerotic lesions: regulation via cd40–cd40 ligand signaling in vitro and in vivo |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192948/ https://www.ncbi.nlm.nih.gov/pubmed/10049948 |
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