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MMP‐1 and MMP‐9 regulate epidermal growth factor‐dependent collagen loss in human carotid plaque smooth muscle cells
Mechanisms underlying the rupture of atherosclerotic plaque, a crucial factor in the development of myocardial infarction and stroke, are not well defined. Here, we examined the role of epidermal growth factor (EGF)‐mediated matrix metalloproteinases (MMP) on the stability of interstitial collagens...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wiley Periodicals, Inc.
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966234/ https://www.ncbi.nlm.nih.gov/pubmed/24744893 http://dx.doi.org/10.1002/phy2.224 |
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author | Rao, Velidi H. Kansal, Vikash Stoupa, Samantha Agrawal, Devendra K. |
author_facet | Rao, Velidi H. Kansal, Vikash Stoupa, Samantha Agrawal, Devendra K. |
author_sort | Rao, Velidi H. |
collection | PubMed |
description | Mechanisms underlying the rupture of atherosclerotic plaque, a crucial factor in the development of myocardial infarction and stroke, are not well defined. Here, we examined the role of epidermal growth factor (EGF)‐mediated matrix metalloproteinases (MMP) on the stability of interstitial collagens in vascular smooth muscle cells (VSMCs) isolated from carotid endarterectomy tissues of symptomatic and asymptomatic patients with carotid stenosis. VSMCs isolated from the carotid plaques of both asymptomatic and symptomatic patients were treated with EGF. The MMP‐9 activity was quantified by gelatin zymography and the analysis of mRNA transcripts and protein for MMP‐9, MMP‐1, EGFR and collagen types I, Col I(α1) and collagen type III, Col III(α1) were analyzed by qPCR and immunofluorescence, respectively. The effect of EGF treatment to increase MMP‐9 activity and mRNA transcripts for MMP‐9, MMP‐1, and EGFR and to decrease mRNA transcripts for Col I(α1) and Col III(α1) was threefold to fourfold greater in VSMCs isolated from the carotid plaques of symptomatic than asymptomatic patients. Inhibitors of EGFR (AG1478) and a small molecule inhibitor of MMP‐9 decreased the MMP9 expression and upregulated Col I(α1) and Col III(α1) in EGF‐treated VSMCs of both groups. Additionally, the magnitude in decreased MMP‐9 mRNA and increased Col I(α1) and Col III(α1) due to knockdown of MMP‐9 gene with siRNA in EGF‐treated VSMCs was significantly greater in the symptomatic group than the asymptomatic group. Thus, a selective blockade of both EGFR and MMP‐9 may be a novel strategy and a promising target for stabilizing vulnerable plaques in patients with carotid stenosis. |
format | Online Article Text |
id | pubmed-3966234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Wiley Periodicals, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-39662342014-03-31 MMP‐1 and MMP‐9 regulate epidermal growth factor‐dependent collagen loss in human carotid plaque smooth muscle cells Rao, Velidi H. Kansal, Vikash Stoupa, Samantha Agrawal, Devendra K. Physiol Rep Original Research Mechanisms underlying the rupture of atherosclerotic plaque, a crucial factor in the development of myocardial infarction and stroke, are not well defined. Here, we examined the role of epidermal growth factor (EGF)‐mediated matrix metalloproteinases (MMP) on the stability of interstitial collagens in vascular smooth muscle cells (VSMCs) isolated from carotid endarterectomy tissues of symptomatic and asymptomatic patients with carotid stenosis. VSMCs isolated from the carotid plaques of both asymptomatic and symptomatic patients were treated with EGF. The MMP‐9 activity was quantified by gelatin zymography and the analysis of mRNA transcripts and protein for MMP‐9, MMP‐1, EGFR and collagen types I, Col I(α1) and collagen type III, Col III(α1) were analyzed by qPCR and immunofluorescence, respectively. The effect of EGF treatment to increase MMP‐9 activity and mRNA transcripts for MMP‐9, MMP‐1, and EGFR and to decrease mRNA transcripts for Col I(α1) and Col III(α1) was threefold to fourfold greater in VSMCs isolated from the carotid plaques of symptomatic than asymptomatic patients. Inhibitors of EGFR (AG1478) and a small molecule inhibitor of MMP‐9 decreased the MMP9 expression and upregulated Col I(α1) and Col III(α1) in EGF‐treated VSMCs of both groups. Additionally, the magnitude in decreased MMP‐9 mRNA and increased Col I(α1) and Col III(α1) due to knockdown of MMP‐9 gene with siRNA in EGF‐treated VSMCs was significantly greater in the symptomatic group than the asymptomatic group. Thus, a selective blockade of both EGFR and MMP‐9 may be a novel strategy and a promising target for stabilizing vulnerable plaques in patients with carotid stenosis. Wiley Periodicals, Inc. 2014-02-10 /pmc/articles/PMC3966234/ /pubmed/24744893 http://dx.doi.org/10.1002/phy2.224 Text en © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Rao, Velidi H. Kansal, Vikash Stoupa, Samantha Agrawal, Devendra K. MMP‐1 and MMP‐9 regulate epidermal growth factor‐dependent collagen loss in human carotid plaque smooth muscle cells |
title | MMP‐1 and MMP‐9 regulate epidermal growth factor‐dependent collagen loss in human carotid plaque smooth muscle cells |
title_full | MMP‐1 and MMP‐9 regulate epidermal growth factor‐dependent collagen loss in human carotid plaque smooth muscle cells |
title_fullStr | MMP‐1 and MMP‐9 regulate epidermal growth factor‐dependent collagen loss in human carotid plaque smooth muscle cells |
title_full_unstemmed | MMP‐1 and MMP‐9 regulate epidermal growth factor‐dependent collagen loss in human carotid plaque smooth muscle cells |
title_short | MMP‐1 and MMP‐9 regulate epidermal growth factor‐dependent collagen loss in human carotid plaque smooth muscle cells |
title_sort | mmp‐1 and mmp‐9 regulate epidermal growth factor‐dependent collagen loss in human carotid plaque smooth muscle cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966234/ https://www.ncbi.nlm.nih.gov/pubmed/24744893 http://dx.doi.org/10.1002/phy2.224 |
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