Galectin-3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Accumulating evidence indicates that galectin-3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1), a receptor for oxLDL uptake, contributes to oxLDL-induced endothelial dysfunction. Whether galectin-3 induces endothelial dysfunction through modulation of LOX-1-mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin-3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX-1. Incubation of HUVECs with galectin-3 increased the expression of LOX-1 in RNA and protein levels. In addition, the expression of LOX-1 induced by oxLDL was promoted by galectin-3. However, pretreatment of LOX-1 antibody reduced LOX-1 mRNA expression level in cells with oxLDL plus galectin-3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen-activated protein kinases followed by nuclear factor kappa B (NF-κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL-8 release were also aggravated in cells treated with galectin-3 combined with oxLDL. Compared to cells treated with galectin-3 plus oxLDL group. We found that LOX-1 antibody mitigated NADPH oxidase activity, p-38 up-regulation, NF-κB activation, and proinflammatory responses in cells treated with galectin-3 combined with oxLDL. We conclude that galectin-3 enhances endothelial LOX-1 expression and propose a new mechanism by which galectin-3 may promote endothelial dysfunction by inducing inflammation via LOX-1/ROS/p38/NF-κB-mediated signaling pathway.
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