The proteoglycan mimecan is associated with carotid plaque vulnerability and increased risk of future cardiovascular death
(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.
(Less)
- author
- organization
-
- EXODIAB: Excellence of Diabetes Research in Sweden
- Cardiovascular Research - Translational Studies (research group)
- Cancer Infection (research group)
- Division of Microbiology, Immunology and Glycobiology - MIG
- Cardiovascular Research - Matrix and Inflammation in Atherosclerosis (research group)
- Diabetes - Cardiovascular Disease (research group)
- EpiHealth: Epidemiology for Health
- Cardiovascular Research - Immunity and Atherosclerosis (research group)
- publishing date
- 2020-11
- 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
- 2024-08-22 05:32:19
@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}}, }