Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Jan Nilsson

Professor

Default user image.

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

Höga nivåer av löslig Lektin-lik receptor-1 för oxiderat LDL är associerat med inflammation i karotisplack och ökad risk för ischemisk stroke

Author

  • Hanna Markstad
  • Andreas Edsfeldt
  • Ingrid Yao Mattison
  • Eva Bengtsson
  • Pratibha Singh
  • Michele Cavalera
  • Giuseppe Asciutto
  • Harry Björkbacka
  • Gunilla Nordin Fredrikson
  • Nuno Dias
  • Petr Volkov
  • Marju Orho-Melander
  • Jan Nilsson
  • Gunnar Engström
  • Isabel Gonçalves

Summary, in English

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.

Department/s

  • Cardiovascular Research - Translational Studies
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • Diabetic Complications
  • Diabetes - Cardiovascular Disease
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Epidemiology

Publishing year

2019-02-19

Language

English

Publication/Series

Journal of the American Heart Association

Volume

8

Issue

4

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • atherosclerosis
  • ischemic stroke
  • lectinlike oxidized low‐density lipoprotein receptor‐1
  • soluble lectinlike oxidized low‐density lipoprotein receptor‐1

Status

Published

Research group

  • Cardiovascular Research - Translational Studies
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • Diabetic Complications
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 2047-9980