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Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice
Proprotein convertases (PCSKs) process matrix metalloproteases and cytokines, but their function in the vasculature is largely unknown. Previously, we demonstrated upregulation of PCSK6 in atherosclerotic plaques from symptomatic patients, localization to smooth muscle cells (SMCs) in the fibrous ca...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225991/ https://www.ncbi.nlm.nih.gov/pubmed/32325687 http://dx.doi.org/10.3390/cells9041009 |
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author | Röhl, Samuel Suur, Bianca E. Lengquist, Mariette Seime, Till Caidahl, Kenneth Hedin, Ulf Arner, Anders Matic, Ljubica Razuvaev, Anton |
author_facet | Röhl, Samuel Suur, Bianca E. Lengquist, Mariette Seime, Till Caidahl, Kenneth Hedin, Ulf Arner, Anders Matic, Ljubica Razuvaev, Anton |
author_sort | Röhl, Samuel |
collection | PubMed |
description | Proprotein convertases (PCSKs) process matrix metalloproteases and cytokines, but their function in the vasculature is largely unknown. Previously, we demonstrated upregulation of PCSK6 in atherosclerotic plaques from symptomatic patients, localization to smooth muscle cells (SMCs) in the fibrous cap and positive correlations with inflammation, extracellular matrix remodeling and cytokines. Here, we hypothesize that PCSK6 could be involved in flow-mediated vascular remodeling and aim to evaluate its role in the physiology of this process using knockout mice. Pcsk6(−/−) and wild type mice were randomized into control and increased blood flow groups and induced in the right common carotid artery (CCA) by ligation of the left CCA. The animals underwent repeated ultrasound biomicroscopy (UBM) examinations followed by euthanization with subsequent evaluation using wire myography, transmission electron microscopy or histology. The Pcsk6(−/−) mice displayed a flow-mediated increase in lumen circumference over time, assessed with UBM. Wire myography revealed differences in the flow-mediated remodeling response detected as an increase in lumen circumference at optimal stretch with concomitant reduction in active tension. Furthermore, a flow-mediated reduction in expression of SMC contractile markers SMA, MYH11 and LMOD1 was seen in the Pcsk6(−/−) media. Absence of PCSK6 increases outward remodeling and reduces medial contractility in response to increased blood flow. |
format | Online Article Text |
id | pubmed-7225991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72259912020-05-18 Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice Röhl, Samuel Suur, Bianca E. Lengquist, Mariette Seime, Till Caidahl, Kenneth Hedin, Ulf Arner, Anders Matic, Ljubica Razuvaev, Anton Cells Article Proprotein convertases (PCSKs) process matrix metalloproteases and cytokines, but their function in the vasculature is largely unknown. Previously, we demonstrated upregulation of PCSK6 in atherosclerotic plaques from symptomatic patients, localization to smooth muscle cells (SMCs) in the fibrous cap and positive correlations with inflammation, extracellular matrix remodeling and cytokines. Here, we hypothesize that PCSK6 could be involved in flow-mediated vascular remodeling and aim to evaluate its role in the physiology of this process using knockout mice. Pcsk6(−/−) and wild type mice were randomized into control and increased blood flow groups and induced in the right common carotid artery (CCA) by ligation of the left CCA. The animals underwent repeated ultrasound biomicroscopy (UBM) examinations followed by euthanization with subsequent evaluation using wire myography, transmission electron microscopy or histology. The Pcsk6(−/−) mice displayed a flow-mediated increase in lumen circumference over time, assessed with UBM. Wire myography revealed differences in the flow-mediated remodeling response detected as an increase in lumen circumference at optimal stretch with concomitant reduction in active tension. Furthermore, a flow-mediated reduction in expression of SMC contractile markers SMA, MYH11 and LMOD1 was seen in the Pcsk6(−/−) media. Absence of PCSK6 increases outward remodeling and reduces medial contractility in response to increased blood flow. MDPI 2020-04-18 /pmc/articles/PMC7225991/ /pubmed/32325687 http://dx.doi.org/10.3390/cells9041009 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Röhl, Samuel Suur, Bianca E. Lengquist, Mariette Seime, Till Caidahl, Kenneth Hedin, Ulf Arner, Anders Matic, Ljubica Razuvaev, Anton Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice |
title | Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice |
title_full | Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice |
title_fullStr | Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice |
title_full_unstemmed | Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice |
title_short | Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice |
title_sort | lack of pcsk6 increases flow-mediated outward arterial remodeling in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225991/ https://www.ncbi.nlm.nih.gov/pubmed/32325687 http://dx.doi.org/10.3390/cells9041009 |
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