Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Schönbeck, Uwe, Mach, François, Sukhova, Galina K., Atkinson, Elizabeth, Levesque, Ethan, Herman, Michael, Graber, Pierre, Basset, Paul, Libby, Peter
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192948/
https://www.ncbi.nlm.nih.gov/pubmed/10049948
_version_ 1782147355450015744
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
work_keys_str_mv AT schonbeckuwe expressionofstromelysin3inatheroscleroticlesionsregulationviacd40cd40ligandsignalinginvitroandinvivo
AT machfrancois expressionofstromelysin3inatheroscleroticlesionsregulationviacd40cd40ligandsignalinginvitroandinvivo
AT sukhovagalinak expressionofstromelysin3inatheroscleroticlesionsregulationviacd40cd40ligandsignalinginvitroandinvivo
AT atkinsonelizabeth expressionofstromelysin3inatheroscleroticlesionsregulationviacd40cd40ligandsignalinginvitroandinvivo
AT levesqueethan expressionofstromelysin3inatheroscleroticlesionsregulationviacd40cd40ligandsignalinginvitroandinvivo
AT hermanmichael expressionofstromelysin3inatheroscleroticlesionsregulationviacd40cd40ligandsignalinginvitroandinvivo
AT graberpierre expressionofstromelysin3inatheroscleroticlesionsregulationviacd40cd40ligandsignalinginvitroandinvivo
AT bassetpaul expressionofstromelysin3inatheroscleroticlesionsregulationviacd40cd40ligandsignalinginvitroandinvivo
AT libbypeter expressionofstromelysin3inatheroscleroticlesionsregulationviacd40cd40ligandsignalinginvitroandinvivo