LOX-1 and mitochondria: an inflammatory relationship

This editorial refers to ‘LOX-1, mtDNA damage, and NLRP3 inflammasome activation in macrophages: implications in atherogenesis’ by Z. Ding et al. , pp. 619–628, this issue. LOX-1 has been described as the responsible receptor for oxidized lipoprotein (oxLDL) binding and internalization, thereby inducing an intracellular oxidative stress response associated with an inflammatory processes occurring in cardiovascular diseases such as atherosclerosis. In the current edition of Cardiovascular Research , Ding et al. 1 report that LOX-1-mediated mitochondrial DNA (mtDNA) damage that escapes autophagy triggers the Nlrp3 inflammasome expression in inflammatory disease states. Oxidative stress occurs during atherogenesis and plays an important role in disease progression by promoting lipid oxidation and the generation of reactive oxygen species (ROS) in the vessel wall. Risk factors, such as hypertension, dyslipidaemia, diabetes mellitus, and smoking, are associated with enhanced oxidative stress.2,3 Accumulation of oxLDLs under the endothelium at atherosclerosis-prone sites is considered as the initial step in atherogenesis.3 Sensing of (oxidized) lipoproteins by endogenous scavenger receptors ( Figure 1 ) has been shown to trigger inflammatory processes, which crucially contributes to atherosclerotic plaque formation.3 The lectin-like oxLDL receptor-1 (LOX-1) is a key scavenger receptor responsible for oxLDL uptake and adjacent foam cell formation. OxLDL itself, as well as other triggers such as ROS, angiotensin II, endothelin, inflammatory cytokines, and shear stress, induces LOX-1 upregulation on vascular cells (endothelial cells, monocytes/macrophages, and vascular smooth …