Oxidized low-density lipoprotein receptor-1 (OLR-1)-induced activation of NF-κB increases intercellular adhesion molecule-1 (ICAM-1) in human vascular smooth muscle cells

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (OLR-1/LOX-1) is known as a scavenger receptor for oxidized low-density lipoprotein (OxLDL) expressed on all type of cells involved in atherosclerosis and restenosis. OLR-1 expressed in endothelial cells and vascular smooth muscle cells induces the expression of pro-inflammatory molecules. Pro-inflammatory molecules such as cytokines and adhesion molecules that cause monocyte recruitment to endothelial cells and vascular smooth muscle cells (VSMCs) may lead endothelial dysfunction, and proliferation and migration of vascular smooth muscle cells. These inflammatory events play an important role in the pathogenesis of atherosclerosis and restenosis. Although the involvement of OLR-1 in the inflammatory responses was well-known in both endothelial cells and VSMCs, the signaling pathway evoked by OLR-1 activation and the effect of this signal transduction in VSMCs are still unclear. In this research, to figure out the role of OLR-1 on the inflammatory events in VSMCs, the expression of a major adhesion molecule, ICAM-1 was examined. By the results, the ICAM-1 expression was increased by OxLDL, which lead to induce monocyte adhesion to VSMCs. Then the downstream signaling pathway leading the induced ICAM-1 expression via OxLDL-induced OLR-1 was investigated, and the involvement of NF-κB and NOX4 activation was confirmed in this signal transduction. From these results, OLR-1 is considered as a key factor mediating the inflammatory events for the progression of atherosclerosis and restenosis by VSMCs. Thus, modulation of the expression of OLR-1 and its downstream signaling pathway can be a clue to regulate the pathogenesis of atherosclerosis and restenosis.