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Photo: KG Pressfoto

Marju Orho-Melander

Professor

Photo: KG Pressfoto

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 of 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