Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation

Abstract

Atherosclerosis is regarded as a dynamic and progressive disease arising from the combination of endothelial dysfunction and inflammation.1–6 This article is the second in a 2-part series examining emerging markers of inflammation and endothelial cell activation. The first article7 provided a brief overview of the link between inflammation, endothelial dysfunction, and atherosclerosis and began the examination of emerging inflammatory mediators. This second article continues with an exploration of more novel markers for cardiovascular disease. ### Lectin-Like Oxidized Low-Density Lipoprotein (LDL) Receptor-1 The endothelial injury, activation, and dysfunction caused by oxidized LDL (oxLDL) in the pathogenesis of atherosclerosis are exerted via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) activation.8,9 LOX-1, initially identified as the major receptor for oxLDL in endothelial cells, can also be expressed in macrophages and smooth muscle cells (SMCs).10–12 It is a type II membrane protein with a C-type lectin–like extracellular domain that can be cleaved, to release the soluble form of LOX-1, by an unknown protease.8 In addition to being the main receptor for oxLDL, LOX-1 has the ability to bind damaged or apoptotic cells, activated platelets, advanced glycation end products, and pathogenic organisms.13–15 Once bound, these ligands can be endocytosed or phagocytosed into the cell. Under physiological conditions, LOX-1 may play a role in host defense or serve to scavenge cellular debris.8 However, in pathological states, LOX-1 may be involved in binding proatherogenic materials, such as oxLDL, that activate the endothelium. With its ability to bind products that induce inflammation and endothelial activation, it is not surprising that elevated LOX-1 expression is observed in both initial and advanced atherosclerotic lesions.16,17 The stage for atherosclerosis is set once endothelial dysfunction occurs. LOX-1 may play a role in initiating and potentiating this crucial first step. Under conditions of hypercholesterolemia, hypertension, and diabetes, disease states that promote vascular injury, …