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Increased proteolytic cleavage of osteoglycin is associated with a stable plaque phenotype and lower risk of cardiovascular events

Al-Sharify, Dania LU ; Nielsen, Signe Holm ; Matthes, Frank LU ; Tengryd, Christoffer LU ; Sun, Jiangming LU orcid ; Genovese, Federica ; Karsdal, Morten A. ; Nilsson, Jan LU ; Goncalves, Isabel LU orcid and Edsfeldt, Andreas LU (2022) In Atherosclerosis 355. p.8-14
Abstract

Background and aims: Extracellular matrix (ECM) remodeling is one of the key components in the formation of vulnerable atherosclerotic plaques and cardiovascular events. We recently showed that the full-length ECM-proteoglycan osteoglycin was associated with plaque vulnerability and future cardiovascular events. In the present study, we aimed to investigate the association of cleaved osteoglycin with plaque phenotype. Methods: Two-hundred human carotid plaques were analyzed by immunohistochemistry. Cleaved osteoglycin and active caspase-3 were assessed by ELISA. ECM components (collagen, elastin and glycosaminoglycans) were assessed by colorimetric assays in plaque tissue homogenates. Matrix metalloproteinases (MMPs) were assessed using... (More)

Background and aims: Extracellular matrix (ECM) remodeling is one of the key components in the formation of vulnerable atherosclerotic plaques and cardiovascular events. We recently showed that the full-length ECM-proteoglycan osteoglycin was associated with plaque vulnerability and future cardiovascular events. In the present study, we aimed to investigate the association of cleaved osteoglycin with plaque phenotype. Methods: Two-hundred human carotid plaques were analyzed by immunohistochemistry. Cleaved osteoglycin and active caspase-3 were assessed by ELISA. ECM components (collagen, elastin and glycosaminoglycans) were assessed by colorimetric assays in plaque tissue homogenates. Matrix metalloproteinases (MMPs) were assessed using Milliplex. MMP-cleavage of osteoglycin and its effect on apoptosis were studied in vitro. Cardiovascular events were recorded during follow-up using national registries. Results: Plaque levels of cleaved osteoglycin were significantly higher in asymptomatic plaques and correlated to α-actin plaque area, collagen, elastin and inversely to lipids, active. caspase-3 and a histological vulnerability index. Cleaved osteoglycin correlated to several MMPs, especially MMP-12, which was also shown to cleave osteoglycin in vitro. In vitro cleavage of osteoglycin was also associated with less smooth muscle cell apoptosis. Patients with high plaque levels of cleaved osteoglycin had a significantly lower risk to suffer from future cardiovascular events. Conclusions: The current study shows that cleaved osteoglycin is associated with a stable plaque phenotype and lower risk for future cardiovascular events. Potentially due to reduced cell apoptosis and ability to retain LDL. These results indicate that targeting the cleavage of osteoglycin may be a potential therapeutic strategy to stabilize plaques.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Biomarkers, Cleaved osteoglycin, Extracellular matrix
in
Atherosclerosis
volume
355
pages
8 - 14
publisher
Elsevier
external identifiers
  • scopus:85134182772
  • pmid:35850021
ISSN
0021-9150
DOI
10.1016/j.atherosclerosis.2022.06.1025
language
English
LU publication?
yes
id
3f9625a2-862f-4a2c-a915-bcb1b3b688ca
date added to LUP
2022-09-27 16:53:04
date last changed
2024-06-27 21:02:02
@article{3f9625a2-862f-4a2c-a915-bcb1b3b688ca,
  abstract     = {{<p>Background and aims: Extracellular matrix (ECM) remodeling is one of the key components in the formation of vulnerable atherosclerotic plaques and cardiovascular events. We recently showed that the full-length ECM-proteoglycan osteoglycin was associated with plaque vulnerability and future cardiovascular events. In the present study, we aimed to investigate the association of cleaved osteoglycin with plaque phenotype. Methods: Two-hundred human carotid plaques were analyzed by immunohistochemistry. Cleaved osteoglycin and active caspase-3 were assessed by ELISA. ECM components (collagen, elastin and glycosaminoglycans) were assessed by colorimetric assays in plaque tissue homogenates. Matrix metalloproteinases (MMPs) were assessed using Milliplex. MMP-cleavage of osteoglycin and its effect on apoptosis were studied in vitro. Cardiovascular events were recorded during follow-up using national registries. Results: Plaque levels of cleaved osteoglycin were significantly higher in asymptomatic plaques and correlated to α-actin plaque area, collagen, elastin and inversely to lipids, active. caspase-3 and a histological vulnerability index. Cleaved osteoglycin correlated to several MMPs, especially MMP-12, which was also shown to cleave osteoglycin in vitro. In vitro cleavage of osteoglycin was also associated with less smooth muscle cell apoptosis. Patients with high plaque levels of cleaved osteoglycin had a significantly lower risk to suffer from future cardiovascular events. Conclusions: The current study shows that cleaved osteoglycin is associated with a stable plaque phenotype and lower risk for future cardiovascular events. Potentially due to reduced cell apoptosis and ability to retain LDL. These results indicate that targeting the cleavage of osteoglycin may be a potential therapeutic strategy to stabilize plaques.</p>}},
  author       = {{Al-Sharify, Dania and Nielsen, Signe Holm and Matthes, Frank and Tengryd, Christoffer and Sun, Jiangming and Genovese, Federica and Karsdal, Morten A. and Nilsson, Jan and Goncalves, Isabel and Edsfeldt, Andreas}},
  issn         = {{0021-9150}},
  keywords     = {{Atherosclerosis; Biomarkers; Cleaved osteoglycin; Extracellular matrix}},
  language     = {{eng}},
  pages        = {{8--14}},
  publisher    = {{Elsevier}},
  series       = {{Atherosclerosis}},
  title        = {{Increased proteolytic cleavage of osteoglycin is associated with a stable plaque phenotype and lower risk of cardiovascular events}},
  url          = {{http://dx.doi.org/10.1016/j.atherosclerosis.2022.06.1025}},
  doi          = {{10.1016/j.atherosclerosis.2022.06.1025}},
  volume       = {{355}},
  year         = {{2022}},
}