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High Levels of Soluble Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 Are Associated With Carotid Plaque Inflammation and Increased Risk of Ischemic Stroke

Markstad, Hanna LU ; Edsfeldt, Andreas LU ; Yao Mattison, Ingrid LU ; Bengtsson, Eva LU orcid ; Singh, Pratibha LU ; Cavalera, Michele LU ; Asciutto, Giuseppe LU ; Björkbacka, Harry LU orcid ; Fredrikson, Gunilla Nordin LU and Dias, Nuno LU orcid , et al. (2019) In Journal of the American Heart Association 8(4).
Abstract

Background When the lectinlike oxidized low-density lipoprotein (ox LDL) receptor-1 ( LOX -1), a scavenger receptor for ox LDL , binds ox LDL , processes leading to endothelial dysfunction and inflammation are promoted. We aimed to study release mechanisms of LOX -1 and how circulating levels of soluble LOX -1 ( sLOX -1) relate to plaque inflammation and future risk for ischemic stroke. Methods and Results Endothelial cells and leukocytes were used to study release of sLOX -1. Plasma levels of sLOX -1 were determined in 4703 participants in the Malmö Diet and Cancer cohort. Incidence of ischemic stroke was monitored. For 202 patients undergoing carotid endarterectomy, levels of sLOX -1 were analyzed in plasma and plaque homogenates and... (More)

Background When the lectinlike oxidized low-density lipoprotein (ox LDL) receptor-1 ( LOX -1), a scavenger receptor for ox LDL , binds ox LDL , processes leading to endothelial dysfunction and inflammation are promoted. We aimed to study release mechanisms of LOX -1 and how circulating levels of soluble LOX -1 ( sLOX -1) relate to plaque inflammation and future risk for ischemic stroke. Methods and Results Endothelial cells and leukocytes were used to study release of sLOX -1. Plasma levels of sLOX -1 were determined in 4703 participants in the Malmö Diet and Cancer cohort. Incidence of ischemic stroke was monitored. For 202 patients undergoing carotid endarterectomy, levels of sLOX -1 were analyzed in plasma and plaque homogenates and related to plaque inflammation factors. Endothelial cells released sLOX -1 when exposed to ox LDL . A total of 257 subjects experienced stroke during a mean follow-up of 16.5 years. Subjects in the highest tertile of sLOX -1 had a stroke hazard ratio of 1.75 (95% CI, 1.28-2.39) compared with those in the lowest tertile after adjusting for age and sex. The patients undergoing carotid endarterectomy had a significant association between plasma sLOX -1 and the plaque content of sLOX -1 ( r=0.209, P=0.004). Plaques with high levels of sLOX -1 had more ox LDL , proinflammatory cytokines, and matrix metalloproteinases. Conclusions Our findings demonstrate that ox LDL induces the release of sLOX -1 from endothelial cells and that circulating levels of sLOX -1 correlate with carotid plaque inflammation and risk for ischemic stroke. These observations provide clinical support to experimental studies implicating LOX -1 in atherosclerosis and its possible role as target for cardiovascular intervention.

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alternative title
Höga nivåer av löslig Lektin-lik receptor-1 för oxiderat LDL är associerat med inflammation i karotisplack och ökad risk för ischemisk stroke
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, ischemic stroke, lectinlike oxidized low‐density lipoprotein receptor‐1, soluble lectinlike oxidized low‐density lipoprotein receptor‐1
in
Journal of the American Heart Association
volume
8
issue
4
article number
e009874
publisher
Wiley-Blackwell
external identifiers
  • pmid:30744454
  • scopus:85061367572
ISSN
2047-9980
DOI
10.1161/JAHA.118.009874
language
English
LU publication?
yes
id
771a5373-c723-407f-8b28-018dd86c04ad
date added to LUP
2019-02-19 07:17:34
date last changed
2024-10-15 19:07:30
@article{771a5373-c723-407f-8b28-018dd86c04ad,
  abstract     = {{<p>Background When the lectinlike oxidized low-density lipoprotein (ox LDL) receptor-1 ( LOX -1), a scavenger receptor for ox LDL , binds ox LDL , processes leading to endothelial dysfunction and inflammation are promoted. We aimed to study release mechanisms of LOX -1 and how circulating levels of soluble LOX -1 ( sLOX -1) relate to plaque inflammation and future risk for ischemic stroke. Methods and Results Endothelial cells and leukocytes were used to study release of sLOX -1. Plasma levels of sLOX -1 were determined in 4703 participants in the Malmö Diet and Cancer cohort. Incidence of ischemic stroke was monitored. For 202 patients undergoing carotid endarterectomy, levels of sLOX -1 were analyzed in plasma and plaque homogenates and related to plaque inflammation factors. Endothelial cells released sLOX -1 when exposed to ox LDL . A total of 257 subjects experienced stroke during a mean follow-up of 16.5 years. Subjects in the highest tertile of sLOX -1 had a stroke hazard ratio of 1.75 (95% CI, 1.28-2.39) compared with those in the lowest tertile after adjusting for age and sex. The patients undergoing carotid endarterectomy had a significant association between plasma sLOX -1 and the plaque content of sLOX -1 ( r=0.209, P=0.004). Plaques with high levels of sLOX -1 had more ox LDL , proinflammatory cytokines, and matrix metalloproteinases. Conclusions Our findings demonstrate that ox LDL induces the release of sLOX -1 from endothelial cells and that circulating levels of sLOX -1 correlate with carotid plaque inflammation and risk for ischemic stroke. These observations provide clinical support to experimental studies implicating LOX -1 in atherosclerosis and its possible role as target for cardiovascular intervention.</p>}},
  author       = {{Markstad, Hanna and Edsfeldt, Andreas and Yao Mattison, Ingrid and Bengtsson, Eva and Singh, Pratibha and Cavalera, Michele and Asciutto, Giuseppe and Björkbacka, Harry and Fredrikson, Gunilla Nordin and Dias, Nuno and Volkov, Petr and Orho-Melander, Marju and Nilsson, Jan and Engström, Gunnar and Gonçalves, Isabel}},
  issn         = {{2047-9980}},
  keywords     = {{atherosclerosis; ischemic stroke; lectinlike oxidized low‐density lipoprotein receptor‐1; soluble lectinlike oxidized low‐density lipoprotein receptor‐1}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{4}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{High Levels of Soluble Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 Are Associated With Carotid Plaque Inflammation and Increased Risk of Ischemic Stroke}},
  url          = {{http://dx.doi.org/10.1161/JAHA.118.009874}},
  doi          = {{10.1161/JAHA.118.009874}},
  volume       = {{8}},
  year         = {{2019}},
}