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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 LU ; Matic, Ljubica and Razuvaev, Anton (2020) In Cells 9(4).
Abstract

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... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pro-protein convertase subtilisin/kexin 6, smooth muscle cells, vessel wall remodeling
in
Cells
volume
9
issue
4
article number
1009
publisher
MDPI AG
external identifiers
  • scopus:85084031008
  • pmid:32325687
ISSN
2073-4409
DOI
10.3390/cells9041009
language
English
LU publication?
yes
id
28edee9b-b0b2-48ea-8162-faaf36cb107e
date added to LUP
2020-05-20 10:30:51
date last changed
2024-04-03 07:18:14
@article{28edee9b-b0b2-48ea-8162-faaf36cb107e,
  abstract     = {{<p>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.</p>}},
  author       = {{Röhl, Samuel and Suur, Bianca E. and Lengquist, Mariette and Seime, Till and Caidahl, Kenneth and Hedin, Ulf and Arner, Anders and Matic, Ljubica and Razuvaev, Anton}},
  issn         = {{2073-4409}},
  keywords     = {{pro-protein convertase subtilisin/kexin 6; smooth muscle cells; vessel wall remodeling}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice}},
  url          = {{http://dx.doi.org/10.3390/cells9041009}},
  doi          = {{10.3390/cells9041009}},
  volume       = {{9}},
  year         = {{2020}},
}