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The proteoglycan mimecan is associated with carotid plaque vulnerability and increased risk of future cardiovascular death

Tengryd, Christoffer LU ; Nielsen, Signe Holm ; Cavalera, Michele LU ; Bengtsson, Eva LU orcid ; Genovese, Federica ; Karsdal, Morten ; Dunér, Pontus LU ; Orho-Melander, Marju LU ; Nilsson, Jan LU and Edsfeldt, Andreas LU , et al. (2020) In Atherosclerosis 313. p.88-95
Abstract

Background and aims: A vulnerable plaque is an atherosclerotic plaque that is rupture-prone with a higher risk to cause cardiovascular symptoms such as myocardial infarction or stroke. Mimecan or osteoglycin is a small leucine-rich proteoglycan, important for collagen fibrillogenesis, that has been implicated in atherosclerotic disease, yet the role of mimecan in human atherosclerotic disease remains unknown. Methods: 196 human atherosclerotic carotid plaques were immunostained for mimecan. Smooth muscle cells, macrophages and intraplaque haemorrhage were also measured with immunohistochemistry. Neutral lipids were stained with Oil Red O and calcium deposits were quantified. Plaque homogenate levels of MCP-1, IL-6 and MIP-1β were... (More)

Background and aims: A vulnerable plaque is an atherosclerotic plaque that is rupture-prone with a higher risk to cause cardiovascular symptoms such as myocardial infarction or stroke. Mimecan or osteoglycin is a small leucine-rich proteoglycan, important for collagen fibrillogenesis, that has been implicated in atherosclerotic disease, yet the role of mimecan in human atherosclerotic disease remains unknown. Methods: 196 human atherosclerotic carotid plaques were immunostained for mimecan. Smooth muscle cells, macrophages and intraplaque haemorrhage were also measured with immunohistochemistry. Neutral lipids were stained with Oil Red O and calcium deposits were quantified. Plaque homogenate levels of MCP-1, IL-6 and MIP-1β were measured using a Proximity Extension Assay and MMP-9 levels were measured using Mesoscale. Glycosaminoglycans, collagen and elastin were assessed by colorimetric assays and TGF-β1, β2 and β3 were measured using a multiplex assay. Mimecan gene expression in THP-1 derived macrophages was quantified by qPCR and protein expression in vitro was visualized with immunofluorescence. Cardiovascular events were registered using medical charts and national registers during follow-up. Results: Mimecan correlated positively with plaque area of lipids, macrophages, intraplaque haemorrhage and inversely with smooth muscle cell staining. Mimecan also correlated positively with plaque levels of MMP-9 and MCP-1. Mimecan was upregulated in THP-1 derived macrophages upon stimulation with MCP-1. Patients with high levels of mimecan (above median) had higher risk for cardiovascular death. Conclusions: This study indicates that mimecan is associated with a vulnerable plaque phenotype, possibly regulated by plaque inflammation. In line, plaque levels of mimecan independently predict future cardiovascular death.

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type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Carotid artery plaque, Extracellular matrix proteins, Inflammation, Proteoglycans
in
Atherosclerosis
volume
313
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85092064512
  • pmid:33032238
ISSN
0021-9150
DOI
10.1016/j.atherosclerosis.2020.09.011
language
English
LU publication?
yes
id
41bd010a-7bc1-4fb1-8a91-441f45ec62aa
date added to LUP
2020-10-29 13:21:37
date last changed
2024-05-29 21:41:43
@article{41bd010a-7bc1-4fb1-8a91-441f45ec62aa,
  abstract     = {{<p>Background and aims: A vulnerable plaque is an atherosclerotic plaque that is rupture-prone with a higher risk to cause cardiovascular symptoms such as myocardial infarction or stroke. Mimecan or osteoglycin is a small leucine-rich proteoglycan, important for collagen fibrillogenesis, that has been implicated in atherosclerotic disease, yet the role of mimecan in human atherosclerotic disease remains unknown. Methods: 196 human atherosclerotic carotid plaques were immunostained for mimecan. Smooth muscle cells, macrophages and intraplaque haemorrhage were also measured with immunohistochemistry. Neutral lipids were stained with Oil Red O and calcium deposits were quantified. Plaque homogenate levels of MCP-1, IL-6 and MIP-1β were measured using a Proximity Extension Assay and MMP-9 levels were measured using Mesoscale. Glycosaminoglycans, collagen and elastin were assessed by colorimetric assays and TGF-β1, β2 and β3 were measured using a multiplex assay. Mimecan gene expression in THP-1 derived macrophages was quantified by qPCR and protein expression in vitro was visualized with immunofluorescence. Cardiovascular events were registered using medical charts and national registers during follow-up. Results: Mimecan correlated positively with plaque area of lipids, macrophages, intraplaque haemorrhage and inversely with smooth muscle cell staining. Mimecan also correlated positively with plaque levels of MMP-9 and MCP-1. Mimecan was upregulated in THP-1 derived macrophages upon stimulation with MCP-1. Patients with high levels of mimecan (above median) had higher risk for cardiovascular death. Conclusions: This study indicates that mimecan is associated with a vulnerable plaque phenotype, possibly regulated by plaque inflammation. In line, plaque levels of mimecan independently predict future cardiovascular death.</p>}},
  author       = {{Tengryd, Christoffer and Nielsen, Signe Holm and Cavalera, Michele and Bengtsson, Eva and Genovese, Federica and Karsdal, Morten and Dunér, Pontus and Orho-Melander, Marju and Nilsson, Jan and Edsfeldt, Andreas and Gonçalves, Isabel}},
  issn         = {{0021-9150}},
  keywords     = {{Atherosclerosis; Carotid artery plaque; Extracellular matrix proteins; Inflammation; Proteoglycans}},
  language     = {{eng}},
  pages        = {{88--95}},
  publisher    = {{Elsevier}},
  series       = {{Atherosclerosis}},
  title        = {{The proteoglycan mimecan is associated with carotid plaque vulnerability and increased risk of future cardiovascular death}},
  url          = {{http://dx.doi.org/10.1016/j.atherosclerosis.2020.09.011}},
  doi          = {{10.1016/j.atherosclerosis.2020.09.011}},
  volume       = {{313}},
  year         = {{2020}},
}