Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is the main endothelial receptor for oxidized low density lipoprotein (OxLDL). LOX-1, is highly expressed in endothelial cells of atherosclerotic lesions, but also in macrophages and smooth muscle cells. LOX-1 expression is upregulated by several inflammatory cytokines (such as TNF-alpha), by oxidative stress, and by pathological conditions, such as dyslipidemia, hypertension, and diabetes. High density lipoprotein (HDL) possess several atheroprotective properties; however under pathological conditions associated with inflammation and oxidative stress, HDL become dysfunctional and exhibit pro-inflammatory properties. In vitro, HDL can be modified by 15-lipoxygenase, an enzyme overexpressed in the atherosclerotic lesions. Here we report that, after modification with 15-lipoxygenase, HDL3 lose their ability to inhibit TNF alpha-induced LOX-1 expression in endothelial cells; in addition, 15LO-modified HDL3 induce LOX-1 mRNA and protein expression and bind to LOX-1 with increased affinity compared to native HDL3. Altogether these findings confirm that 15LO-modified HDL3 possess a pro-atherogenic role. (C) 2012 Elsevier Inc. All rights reserved.