Upregulation of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) expression in human endothelial cells by modified high density lipoproteins

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-α), 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 TNFα-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.

► LOX-1, the main endothelial receptor for OxLDL, is involved in the induction of endothelial dysfunction.
► HDL3 modified with 15-lipoxygenase (15LO) upregulate the expression of LOX-1 in endothelial cells.
► HDL3 modified with 15LO interact with LOX-1 inducing the expression of ICAM-1.
► HDL3 modified with 15LO might contribute to the activation and dysfunction of endothelial cells.