Abstract
Endothelial injury and dysfunction followed by endothelial activation and inflammatory cell recruitment are factors contributing to the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) promotes inflammation during atherogenesis and lipid deposition in the arterial wall. We observed that stimulation of human umbilical vein endothelial cells (HUVECs) with ox-LDL activated pro-inflammatory cytokine production and apoptosis, inhibited cell migration, and upregulated T-cell immunoglobulin and mucin domain 3 (Tim-3) expression. Tim-3, in turn, protected HUVECs from ox-LDL-induced apoptosis via the JNK pathway and reversed the inhibition of migration. Tim-3 also inhibited ox-LDL-induced inflammatory cytokine production by suppressing NF-κB activation. In addition, Tim-3 increased production of type 2 T helper cells (Th2) and regulatory T cell (Treg)-associated cytokines. Blocking Tim-3 reversed its effects on the inflammatory response to ox-LDL. Thus, Tim-3 signaling may be a "self-control" mechanism in ox-LDL-triggered inflammation in HUVECs. These results identify Tim-3 as a factor in HUVEC activity and suggest its potential in the treatment of atherosclerosis.