Mannose-Binding Lectin Reduces Oxidized Low-Density Lipoprotein Induced Vascular Endothelial Cells Injury by Inhibiting LOX1-ox-LDL Binding and Modulating Autophagy

Abstract

Objective: To investigate the role of mannose-binding lectin (MBL) in modulating autophagy and protecting endothelial cells (ECs) from oxidized low-density lipoprotein (ox-LDL)-induced injury. Methods: Serum MBL concentration and carotid intima-media thickness (cIMT) were measured in 94 obese and 105 healthy children. ECs were transfected with MBL over-expression plasmid, LOX1 was knocked-down to explore the protective role of MBL in ox-LDL induced ECs injury. Dendritic cells (DCs) were co-cultured with ECs, and inflammatory factors, DC maturation, and autophagy was assessed. WT and ApoE−/− mice were fed with a high fat diet (HFD) with or without MBL-adenovirus injection for 16 weeks and aortic vascular endothelial tissue was isolated, then atherosclerotic plaque, cell injury and autophagy were analyzed. Results: Serum MBL concentration in obese children was lower than healthy controls and was negatively correlated with cIMT. The uptake of ox-LDL was decreased in LOX1 knock-down ECs. MBL over-expression in vitro inhibited LOX1-ox-LDL binding. Both LOX1 knock-down and MBL over-expression can ameliorate EC autophagy and cell injury. MBL over-expression in vivo alleviated atherosclerotic plaque formation, influenced DC maturation and down-regulated IL-6, IL-12, and TNF-a levels. Conclusions: MBL exerts a protective role in ox-LDL-induced EC injury by modulating DC maturation and EC autophagy via inhibiting LOX1-ox-LDL binding.

Keywords

• mannose-binding lectin
• endothelial cells injury
• autophagy
• LOX1
• atherosclerosis