Open AccessHigh Levels of Soluble Lectinlike Oxidized Low‐Density Lipoprotein Receptor‐1 Are Associated With Carotid Plaque Inflammation and Increased Risk of Ischemic Stroke
Author(s) -
Markstad Hanna,
Edsfeldt Andreas,
Yao Mattison Ingrid,
Bengtsson Eva,
Singh Pratibha,
Cavalera Michele,
Asciutto Giuseppe,
Björkbacka Harry,
Fredrikson Gunilla Nordin,
Dias Nuno,
Volkov Petr,
OrhoMelander Marju,
Nilsson Jan,
Engström Gunnar,
Gonçalves Isabel
Publication year - 2019
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.118.009874
Subject(s) - medicine , inflammation , carotid endarterectomy , proinflammatory cytokine , stroke (engine) , scavenger receptor , lipoprotein , endarterectomy , endothelial dysfunction , receptor , vulnerable plaque , hazard ratio , gastroenterology , endocrinology , cholesterol , carotid arteries , confidence interval , engineering , mechanical engineering
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.