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Elevated asporin expression in human atherosclerotic plaques promotes their stability and reduces the risk for cardiovascular events

Fountas, Panagiotis LU ; Gialeli, Chrysostomi LU ; Thorsen, Nicoline W LU ; Acoba, Dianne LU orcid ; Sun, Jiangming LU orcid ; Gamon, Luke F LU ; Shami, Annelie LU orcid ; Nitulescu, Mihaela LU ; Persson, Ana LU and Bengtsson, Eva LU orcid , et al. (2026) In Cardiovascular Research p.1-14
Abstract

AIMS: Vascular atherosclerotic calcification is a pathological process marked by the abnormal deposition of calcium minerals in the intima. Asporin (ASPN) is a small leucine-rich proteoglycan which interacts with collagen and calcium. Due to its role in matrix mineralization, we hypothesized that ASPN might act as a regulator of vascular calcification, thereby promoting atherosclerotic plaque stability.

METHODS AND RESULTS: ASPN protein, analyzed by ELISA, was quantified in 176 carotid endarterectomy plaques (Carotid Plaque Imaging Project cohort, including 98 patients with cerebrovascular symptoms and 78 asymptomatic patients). Plaque composition was assessed by histological, biochemical and immunological assays, along with bulk... (More)

AIMS: Vascular atherosclerotic calcification is a pathological process marked by the abnormal deposition of calcium minerals in the intima. Asporin (ASPN) is a small leucine-rich proteoglycan which interacts with collagen and calcium. Due to its role in matrix mineralization, we hypothesized that ASPN might act as a regulator of vascular calcification, thereby promoting atherosclerotic plaque stability.

METHODS AND RESULTS: ASPN protein, analyzed by ELISA, was quantified in 176 carotid endarterectomy plaques (Carotid Plaque Imaging Project cohort, including 98 patients with cerebrovascular symptoms and 78 asymptomatic patients). Plaque composition was assessed by histological, biochemical and immunological assays, along with bulk RNA sequencing, to investigate the role of ASPN in atherosclerosis. Patients donating plaques were followed up for postoperative cardiovascular events, median follow-up 6.58 years. The effect of ASPN on smooth muscle cell differentiation and matrix mineralization was investigated in vitro using human vascular smooth muscle cells overexpressing ASPN. Increased ASPN protein levels were observed in plaques from asymptomatic patients compared to patients with cerebrovascular symptoms. ASPN protein levels were positively associated with markers of plaque stability and regulation of extracellular matrix remodelling while showing an inverse relationship with calcification. Patients with high intraplaque ASPN had a lower risk for future cardiovascular events. Mechanistically, ASPN overexpression in vascular smooth muscle cells reduced matrix mineralization in vitro, supporting its potential role in plaque stabilization.

CONCLUSION: ASPN is a regulator of vascular calcification in atherosclerosis, promoting a plaque phenotype that is less prone to rupture. Additionally, high ASPN levels are associated with fewer future cardiovascular events.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Cardiovascular Research
article number
cvag015
pages
1 - 14
publisher
Oxford University Press
external identifiers
  • pmid:41557654
ISSN
1755-3245
DOI
10.1093/cvr/cvag015
language
English
LU publication?
yes
additional info
© The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology.
id
5dd0a1db-8486-4539-9d5c-948d6bcf490f
date added to LUP
2026-02-02 20:42:56
date last changed
2026-02-03 07:23:47
@article{5dd0a1db-8486-4539-9d5c-948d6bcf490f,
  abstract     = {{<p>AIMS: Vascular atherosclerotic calcification is a pathological process marked by the abnormal deposition of calcium minerals in the intima. Asporin (ASPN) is a small leucine-rich proteoglycan which interacts with collagen and calcium. Due to its role in matrix mineralization, we hypothesized that ASPN might act as a regulator of vascular calcification, thereby promoting atherosclerotic plaque stability.</p><p>METHODS AND RESULTS: ASPN protein, analyzed by ELISA, was quantified in 176 carotid endarterectomy plaques (Carotid Plaque Imaging Project cohort, including 98 patients with cerebrovascular symptoms and 78 asymptomatic patients). Plaque composition was assessed by histological, biochemical and immunological assays, along with bulk RNA sequencing, to investigate the role of ASPN in atherosclerosis. Patients donating plaques were followed up for postoperative cardiovascular events, median follow-up 6.58 years. The effect of ASPN on smooth muscle cell differentiation and matrix mineralization was investigated in vitro using human vascular smooth muscle cells overexpressing ASPN. Increased ASPN protein levels were observed in plaques from asymptomatic patients compared to patients with cerebrovascular symptoms. ASPN protein levels were positively associated with markers of plaque stability and regulation of extracellular matrix remodelling while showing an inverse relationship with calcification. Patients with high intraplaque ASPN had a lower risk for future cardiovascular events. Mechanistically, ASPN overexpression in vascular smooth muscle cells reduced matrix mineralization in vitro, supporting its potential role in plaque stabilization.</p><p>CONCLUSION: ASPN is a regulator of vascular calcification in atherosclerosis, promoting a plaque phenotype that is less prone to rupture. Additionally, high ASPN levels are associated with fewer future cardiovascular events.</p>}},
  author       = {{Fountas, Panagiotis and Gialeli, Chrysostomi and Thorsen, Nicoline W and Acoba, Dianne and Sun, Jiangming and Gamon, Luke F and Shami, Annelie and Nitulescu, Mihaela and Persson, Ana and Bengtsson, Eva and Davies, Michael J and Edsfeldt, Andreas and Goettsch, Claudia and Gonçalves, Isabel}},
  issn         = {{1755-3245}},
  language     = {{eng}},
  month        = {{01}},
  pages        = {{1--14}},
  publisher    = {{Oxford University Press}},
  series       = {{Cardiovascular Research}},
  title        = {{Elevated asporin expression in human atherosclerotic plaques promotes their stability and reduces the risk for cardiovascular events}},
  url          = {{http://dx.doi.org/10.1093/cvr/cvag015}},
  doi          = {{10.1093/cvr/cvag015}},
  year         = {{2026}},
}