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

BACKGROUND: When the lectinlike oxidized low‐density lipoprotein (oxLDL) receptor‐1 (LOX‐1), a scavenger receptor for oxLDL, binds oxLDL, 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 oxLDL. 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 oxLDL, proinflammatory cytokines, and matrix metalloproteinases. CONCLUSIONS: Our findings demonstrate that oxLDL 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.