Tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells
Metrics: PDF 664 views | HTML 975 views | ?
Ming-Ke Qiu1,*, Song-Cun Wang2,*, Yong Tang3,*, Chang Pan1, Yang Wang1, Shu-Qing Wang1, Zhi-Wei Quan1 and Jing-Min Ou1
1Department of General Surgery, Xinhua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, China
2Department of Gynecology, Xinhua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, China
3Department of Cardiology, Xinhua Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, China
*These authors have contributed equally to this work
Zhi-Wei Quan, email: email@example.com
Jing-Min Ou, email: firstname.lastname@example.org
Keywords: atherosclerosis, Tim-3, ox-LDL, inflammatory reaction, HUVEC
Received: November 08, 2016 Accepted: April 18, 2017 Published: May 09, 2017
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.